tbuckley/cabot-search huggingface dataset:
The effects of 5-azacytidine and 5-azadeoxycytidine on chromosome structure and function: Implications for methylation-associated cellular processes
Authors: Thomas Haaf
Journal: Pharmacology & Therapeutics (1995)

5-Azacytidine (5-aza-C) analogs demonstrate a remarkable ability to induce heritable changes in gene and phenotypic expression. These cellular processes are associated with the demethylation of specific DNA sequences. On the other hand, 5-aza-C analogs have dramatic effects on chromosomes, leading to decondensation of chromatin structure, chromosomal instability and an advance in replication timing. Condensation inhibition of genetically inactive chromatin occurs when the DNA is still hemimethylated or fully methylated. In cell cultures prolonged for several replication cycles, chromosomal rearrangements and instability affect the 5-aza-C-sensitive regions. Moreover, the normally late-replicating inactive chromatin undergoes a transient temporal shift to an earlier DNA replication, characteristic of activatable chromatin. zThe induced alterations of chromosome structure and behavior may trigger the 5-aza-C-dependent process of cellular reprogramming. Apart from their differentiating and gene-modifying effects, 5-aza-C analogs can tumorigenically transform cells and modulate their metastatic potential. High doses of 5-aza-C analogs have cytotoxic and antineoplastic activities.
High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.
Authors: K Decochez, J Tits, J L Coolens, L Van Gaal, G Krzentowski, F Winnock, E Anckaert, I Weets, D G Pipeleers, F K Gorus
Journal: Diabetes Care (2000)

OBJECTIVE: To study the presence and levels of GAD65 antibodies (GADA), IA-2 antibodies (IA-2-A), and islet cell antibodies (ICA) during the first years after clinical onset of type 1 diabetes in relation to age at diagnosis. RESEARCH DESIGN AND METHODS: Type 1 diabetic patients (n = 194) &amp;lt;40 years of age were consecutively recruited at the time of diagnosis by the Belgian Diabetes Registry and followed during the first 4 years of insulin treatment. ICA were determined by indirect immunofluorescence assay and IA-2-A, GADA, and insulin autoantibodies by a radioligand assay. RESULTS: Overall, 94% of initially antibody-positive patients (n = 180) remained positive for at least 1 antibody type 4 years after diagnosis. In the case of diagnosis after 7 years of age, GADA, IA-2-A, and ICA persisted in 91, 88, and 71%, respectively, of the initially antibody-positive patients. Antibody persistence was lower in those diagnosed at &amp;lt;7 years of age, amounting to 60% for GADA, 71% for IA-2-A, and 39% for ICA. In 57% of the initially antibody-positive patients, at least 1 type of autoantibody reached peak values after diagnosis. This occurred more frequently for clinical onset after 7 years of age and more often for GADA (49%) than for IA-2-A (29%) or ICA (19%). Of the patients, 24% that were negative for GADA at onset became GADA-positive during the following 4 years. Among the 7% initially antibody-negative patients, 2 of 14 subjects developed antibodies after clinical onset. CONCLUSIONS: In particular, for diagnosis after 7 years of age, islet cell-specific autoantibodies generally persist for many years after diagnosis. There is also a high frequency of increasing antibody levels and of conversion to antibody positivity in the first 4 years after diagnosis and start of insulin treatment. Thus, determination of antibodies at diagnosis can underestimate the number of cases with autoimmune type 1 diabetes, in particular with assays of lower sensitivity. The divergent temporal patterns of ICA, GADA, and IA-2-A suggest that the ICA test recognizes other antibody specificities besides GADA and IA-2-A and reflects other autoimmune processes; it also indicates that GADA assays have a higher diagnostic sensitivity in the period after clinical onset.
Myocardial Viability Testing and the Effect of Early Intervention in Patients With Advanced Left Ventricular Systolic Dysfunction
Authors: Khaldoun G. Tarakji, Richard Brunken, Patrick M. McCarthy, M. Obadah Al-Chekakie, Ahmed Abdel-Latif, Claire E. Pothier, Eugene H. Blackstone, Michael S. Lauer
Journal: Circulation (2006)

The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography (PET) with fluorodeoxyglucose (FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization.We analyzed the survival of 765 consecutive patients (age 64+/-11 years, 80% men) with advanced left ventricular systolic dysfunction (ejection fraction < or =35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention (surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients (30%) underwent early intervention (188 [25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42 [5%] had percutaneous revascularization); 535 (70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death (3-year mortality rate of 15% versus 35%, propensity adjusted hazard ratio 0.52, 95% CI 0.33 to 0.81, P=0.0004).Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.
Impact of disease severity on outcome of antiviral therapy in treatment‐naïve patients with chronic hepatitis C†
Authors: Johan Westin, Kristoffer Hellstrand, Åsa Alsiö, Magdalena Ydreborg, Carlo Ferrari, Avidan U. Neumann, Jean‐Michel Pawlotsky, Solko W. Schalm, Stefan Zeuzem, Elke Verhey‐Hart, Martin Lagging
Journal: Hepatology (2007)

We read with interest the article by Everson et al.1 The authors convincingly demonstrate that disease severity, as measured by both degree of liver fibrosis and platelet count, has a major impact on the rate of sustained viral response (SVR) following therapy with peginterferon α-2a and ribavirin among patients with advanced chronic HCV infection who have formerly not responded to interferon therapy. Previous reports indicate SVR rates of 43%–75% among treatment-naïve patients with cirrhosis and/or bridging fibrosis after combination therapy with peginterferon and ribavirin,2-4 with the highest response rates noted among patients infected with genotypes 2 or 3.3 The impact of portal hypertension with splenomegaly as reflected by the platelet count was, however, not reported in these studies. In a European HCV multicenter treatment study,5 we treated 270 treatment-naïve HCV-infected patients with peginterferon α-2a and ribavirin. Eighty of these patients had either bridging fibrosis (Ishak stage 3–4) or cirrhosis (Ishak stage 5–6) in their pretreatment liver biopsies. Their SVR rates with regards to genotype and baseline platelet counts and fibrosis stage are summarized in Table 1. Interestingly, patients infected with genotype 1 who had both bridging fibrosis and platelet count ≤125,000/mm3 achieved SVR, compared to none of 5 patients infected with genotype 1 who had cirrhosis and low platelet count (P = 0.0476, Fisher's exact test). Disease severity, however, had less impact on SVR among patients infected with genotypes 2 or 3. In conclusion, these findings support the results presented by Everson et al. that disease severity as measured by both fibrosis stage and platelet count is a major determinant of treatment outcome in patients with advanced chronic hepatitis C, especially those infected with genotype 1, even in patients previously naïve to treatment. Johan Westin*, Kristoffer Hellstrand*, Åsa Alsiö*, Magdalena Ydreborg*, Carlo Ferrari , Avidan U. Neumann , Jean-Michel Pawlotsky?, Solko W. Schalm?, Stefan Zeuzem**, Elke Verhey-Hart?, Martin Lagging*, * Department of Infectious Diseases, University of Göteborg, Sweden, Azienda Ospedaliera di Parma, Parma, Italy, Bar-Ilan University, Ramat-Gan, Israel, ? Hôpital Henri Mondor—Université Paris XII, Creteil, France, ? University Hospital Rotterdam Dijkzigt, Rotterdam, The Netherlands, ** Saarland University Hospital, Homburg/Saar, Germany.
IVF Registry Notes More Centers, More Births, Slightly Improved Odds
Authors: Chris Anne Raymond
Journal: JAMA (1988)

RECENTLY RELEASED data from 41 of the country's estimated 160 in vitro fertilization clinics indicate that the technique's success rate is improving somewhat. In 1986, 485 clinical pregnancies occurred in 3055 women (15.9%), up from 337 pregnancies in 2475 women (13.6%) in 1985 (<i>Fertil Steril</i>1988;49:212-215). Data included in the registry were reported voluntarily by the clinics, so the success rates or numbers of live births at clinics not participating in the registry are unknown. In releasing the data, the American Fertility Society cited overall success rates for 1985 and 1986 as 14.1% and 16.9%, respectively. Those figures are based on the number of clinical pregnancies per embryo transfer, figures which some fertility specialists think may be misinterpreted by patients (<i>JAMA</i>1988;259:464-469). The reason for this is because embryo transfer is the final step in a many-step procedure to achieve pregnancy. Using clinical pregnancies in the numerator and the number
Significant phenylalanine hydroxylation in vivo in patients with classical phenylketonuria.
Authors: G N Thompson, D Halliday
Journal: Journal of Clinical Investigation (1990)

Indirect measurements have previously suggested that patients with classical phenylketonuria (PKU) do not convert significant amounts of phenylalanine to tyrosine. Low-dose continuous infusion techniques employing [2H5]phenylalanine and [2H2]tyrosine were used to quantitate in vivo phenylalanine hydroxylation in 10 subjects with classical phenylketonuria, 2 with hyperphenylalaninemia (HPA), and 7 controls. Plasma phenylalanine concentration ranged from 523 to 1,540 mumols/liter in PKU, 402 to 533 in HPA, and 49 to 54 in controls. Subjects with classical PKU hydroxylated mean +/- SD 4.8 +/- 2.2 mumols/kg per h (range 0.9-8.4) of phenylalanine to tyrosine and those with HPA 4.4 and 5.3, respectively. These rates were substantial in comparison with those in controls (6.3 +/- 1.6, 3.2-8.2). The significant hydroxylation in PKU and HPA subjects is likely to result from induction of activity of tyrosine hydroxylase towards phenylalanine by the greatly elevated phenylalanine concentration. The presence of such activity in PKU suggests that therapy aimed at promotion of this usually latent hydroxylating capacity may be a future alternative to dietary treatment of PKU.
Low-Intensity Laser Therapy for Painful Symptoms of Diabetic Sensorimotor Polyneuropathy
Authors: Lorne H. Zinman, Mylan Ngo, Eduardo T. Ng, Khin T. Nwe, Sven Gogov, Vera Bril
Journal: Diabetes Care (2004)

OBJECTIVE—Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP. RESEARCH DESIGN AND METHODS—We conducted a randomized, double-masked, sham therapy-controlled clinical trial in 50 patients with painful DSP diagnosed with the Toronto Clinical Neuropathy Score. All patients received sham therapy over a 2-week baseline period and were then randomized to receive biweekly sessions of either sham or LILT for 4 weeks. The primary efficacy parameter was the difference in the weekly mean pain scores on a visual analog scale (VAS). RESULTS—The patients had similar baseline characteristics for pain intensity, HbA1c, and duration of DSP. Both groups noted a decrease in weekly mean pain scores during sham treatment. After the 4-week intervention, the LILT group had an additional reduction in weekly mean pain scores of −1.0 ± 0.4 compared with −0.0 ± 0.4 for the sham group (P = 0.07). LILT had no effect on the Toronto Clinical Neuropathy Score, nerve conduction studies, sympathetic skin response, or quantitative sensory testing. CONCLUSIONS—Although an encouraging trend was observed with LILT, the study results do not provide sufficient evidence to recommend this treatment for painful symptoms of DSP.
THAT ADVERTISING CIRCULAR.
Authors: J. B. Hamilton
Journal: JAMA (1898)

We reproduce the following from<i>Printer's Ink</i>of May 25, which is self-explanatory. With this we close the subject. <h3>TO RIGHT A WRONG.</h3> "The Journal of the American Medical Association," Published Weekly under Direction of Board of Trustees. 61 Market Street.Chicago, May 16, 1898. <h3>Geo. P. Rowell Advertising Co:</h3> Replying to your letter of May 14, I have to say that on examination of the blank sent to this office concerning the alleged agreement to publish the Ripan's Chemical Co.'s prepared medicine, I find that the blank was never in this office to the knowledge of any responsible person connected with it. The handwriting in the blank is not that of any person connected with this office. The typewriting does not conform to that used on the machines in this office. Furthermore, the blank is not signed. The alleged rate shows that it is put in as a monthly
PLATELET-DERIVED GROWTH FACTORS AS POSSIBLE MEDIATORS OF VASCULAR PROLIFERATION IN THE SPORADIC HAEMOLYTIC URAEMIC SYNDROME
Authors: Michael Levin, MartinD.S. Walters, MichaelD. Waterfield, Paul Stroobant, DorothyJ. Cheng, T.Martin Barratt
Journal: The Lancet (1986)
India considers new polio vaccine, kindling debate on strategy
Authors: G. Mudur
Journal: BMJ (2008)

India’s health ministry is evaluating a proposal to introduce the injectable polio vaccine next year in one region of India, questioning for the first time its three decade policy of using only oral vaccines to eradicate polio.

The India Expert Advisory Group on Polio Eradication has recommended adding the injectable vaccine to existing oral vaccine campaigns in the nine worst affected districts of the northern state of Uttar Pradesh.

The group, a panel of experts from India, the World Health Organization, and other agencies, has advised that two campaigns be run, six months apart, in which the injectable vaccine is given to children aged between 3 months and 24 months. 

India accounted for 874 of the total of 1208 polio cases last year in the four countries with endemic polio (the others being Pakistan, Nigeria, and Afghanistan). Despite numerous campaigns with the oral vaccine, polio has persisted in the states of …
EU must reform clinical trial regulation, warn medical research bodies
Authors: S. Mayor
Journal: BMJ (2011)

Medical research organisations are urging the European Union to review the regulation of clinical trials because they say that excessive bureaucracy is hampering research into new treatments without enhancing the safety of patients.

Sixteen research organisations, including the European Organisation for Research and Treatment of Cancer, Germany’s KKS Network of Clinical trials in Germany, and the UK Medical Research Council, have sent a joint statement to the European Commission and members of the European parliament. It outlines how the European Clinical Trials Directive—which sets out the legal requirements for conducting clinical trials throughout the European Union—should be revised to streamline the process of approval of clinical trials.

The Clinical Trials Directive 2001/20/EC …
Review of randomised controlled trials of traditional Chinese medicine
Authors: J.-L. Tang, S.-Y. Zhan, E. Ernst
Journal: BMJ (1999)

Many randomised controlled trials have been conducted in China to evaluate the effectiveness of traditional Chinese medicine, but much of the information is inaccessible to Western doctors. We estimated the total number of randomised controlled trials published in China and identified problems in applying such methodology to the evaluation of traditional Chinese medicine, which would serve as preparatory work for systematic review and dissemination of the randomised evidence for such medicine.

We randomly selected 28 journals using stratified sampling from a total of 100 Chinese journals of traditional Chinese medicine (4 national, 10 university, 10 provincial or regional, and 4 specialist journals). After special training, eight fifth year medical students (working in pairs) hand searched all the issues of the journals published before 1 January 1997 to identify randomised controlled trials. Discrepancies were settled by one of the principal investigators (S-YZ). Data on methodological quality of randomised controlled trials were extracted from 414 full length articles …
Diagnosis of ovarian cancer in primary care
Authors: J. Austoker
Journal: BMJ (2009)

Persistent abdominal distension carries the highest predictive value

Worldwide, more than 200 000 new cases of ovarian cancer occur each year, and these account for around 4% of all cancers diagnosed in women.1 Overall the five year survival rate from ovarian cancer is poor at around 30-40%. For women diagnosed with early stage disease, the five year survival rate is over 70%, but only a fifth of cases are diagnosed early.2 For women with late stage disease, the five year survival rate is around 15%. No effective screening test is available.

Earlier identification of symptoms could improve prognosis,3 4 and in the linked case control study (doi:10.1136/bmj.b2998), Hamilton and colleagues report the predictive value of symptoms in diagnosing ovarian cancer in primary care.5 

The late stage of presentation has been blamed on the insidious nature of the disease, which has vague non-specific symptoms. Historically, ovarian cancer has been referred to as the “silent killer” because it was believed that no symptoms were evident in early disease. Deciding which patients to refer to a specialist is difficult for primary care doctors because the presenting symptoms of ovarian cancer …
Self-Expanding Metallic Coil Stents for Palliation of Esophageal Carcinoma: Two Cases of Decisive Stent Dysfunction
Authors: Chr. Löser, U. R. Fölsch
Journal: Endoscopy (1996)

Two cases of different dysfunctions of self-expanding nickel-titanium coil stents are described here. In the first case, a metallic coil stent was placed in a 8-cm circular rigid stenosis of the mid-esophagus caused by a squamous-cell carcinoma (T3 N1 M1), and seven weeks later, the stent lumen was completely occluded by massive tumor ingrowth through inadequtely adapted single coil wires. In the second case, the caudal and cranial ends of the stent became increasingly invaginated after initially adequate stent expansion, resulting in a shortening of the stent to about two-thirds of its intended size, with subsequent complete luminal obstruction at both ends of the stent due to tumor overgrowth. These two examples of different stent dysfunction correspond to similar observations by other investigators. Further investigations in a large series of stent insertions have to be performed before general conclusion can be drawn as to the clinical efficacy of metallic coil stents for endoscopic palliation of esophageal carcinoma.
Cancer mortality among coke oven workers.
Authors: C K Redmond
Journal: Environmental Health Perspectives (1983)

The OSHA standard for coke oven emissions, which went into effect in January 1977, sets a permissible exposure limit to coke oven emissions of 150 micrograms/m3 benzene-soluble fraction of total particulate matter (BSFTPM). Review of the epidemiologic evidence for the standard indicates an excess relative risk for lung cancer as high as 16-fold in topside coke oven workers with 15 years of exposure or more. There is also evidence for a consistent dose-response relationship in lung cancer mortality when duration and location of employment at the coke ovens are considered. Dose-response models fitted to these same data indicate that, while excess risks may still occur under the OSHA standard, the predicted levels of increased relative risk would be about 30-50% if a linear dose-response model is assumed and 3-7% if a quadratic model is assumed. Lung cancer mortality data for other steelworkers suggest the predicted excess risk has probably been somewhat overestimated, but lack of information on important confounding factors limits further dose-response analysis.
There is nothing like the real thing
Authors: M. E Black
Journal: BMJ (2008)

I have been involved in competitive sailing for years. Equipment, tactics, team psychology, logistics, nutrition, medical support—I can discuss all these and give you my measured and informed opinion. Give me a team trip to organise or a race strategy to review and I can throw my weight around. For I have seen it all either from the harbour, through my binoculars, or up close from a judge’s boat. But this week was the first time I had competed. And, believe me, nothing had prepared me for the real thing: …