tbuckley/cabot-search huggingface dataset:
Dendritic cell vaccine treatment for indolent B cell non-hodgkin lymphoma: clinical trial in progress
Authors: Yi Lin, Thomas Atwell, Adam Weisbrod, Mary Maas, Adam Armstrong, Michael Deeds, Peggy Bulur, Michael Gustafson, Zhe Zhang, Louis Porrata, Svetomir Markovic, Patrick Johnston, Ivana Micallef, David Inwards, Joseph Colgan, Stephen Ansell, Dennis Gastineau, Allan Dietz, Thomas Witzig
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts We present the preliminary results of our clinical trial testing 2 vaccine strategies in patients with indolent B cell non-Hodgkin lymphoma (NHL; [NCT01239875][1], <http://clinicaltrials.gov>). The primary objective is to determine the safety and feasibility of the vaccine
Genetic variants of STAT4 associated with rheumatoid arthritis in persons of Asian and European ancestry do not replicate in African Americans
Authors: J. M. Kelley, L. B. Hughes, A. Malik, M. I. Danila, Y. Edberg, G. S. Alarcon, D. L. Conn, B. L. Jonas, L. F. Callahan, E. A. Smith, R. D. Brasington, J. C. Edberg, R. P. Kimberly, L. W. Moreland, S. L. Bridges
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) was recently genetically associated with signal transducer and activator of transcription 4 ( STAT4 ) in white individuals.1 This study included over 6000 participants to produce an odds ratio (OR) of 1.32 at rs7574865 (p<0.001). Three other single-nucleotide polymorphisms (SNP) located in intron 3 of STAT4 (rs8179673, rs10181656, rs6752770), three SNP in strong linkage disequilibrium with rs7574865 (r2=1.0; rs7582694, rs7568275, rs11889341) and a haplotype driven by the T allele of rs7574865 are also associated with RA susceptibility.1 Association with rs7574865 replicated in several Asian and European-based populations (see table 1). As racial/ethnic differences have been observed at RA susceptibility loci, including CTLA4, PADI4, PTPN22, RUNX1 and SLC22A4 , we aimed to determine if an association with these STAT4 markers and RA susceptibility is consistent in African Americans.

View this table:

Table 1 
Previously published genetic associations with the T allele of rs7574865 …
Gangrene Complicating Pregnancies.
Authors: Q. C. Smith
Journal: JAMA (1901)

Austin, Texas, Oct. 11, 1901. <h3>To the Editor:</h3> —For the benefit of the statistic-pathologist, allow me to report that several years ago, a primipara, of this city, lost one of her feet, and part of the ankle, as a result of gangrene, complicating parturition. The patient fully recovered, and has since borne five healthy children, all of whom are now strong and well. Personal observations lead us to believe that such complications are not so rare, or so fatal, as many writers would have us to believe.
Reasons to be cautious about competing interests
Authors: R. Smith
Journal: BMJ (2015)

I agree that disclosure on its own is not an adequate response to competing interests.1 There has to be a point at which the competing interest is so extreme that the person has to be ruled out of the article, review, decision, or whatever the activity. But defining that point is notoriously hard.

The subheading of the editorial says “zero tolerance,” but it cannot really mean zero tolerance because that would rule out any author who had been given a pen, a pad, or lunch by a company. …
Informed Consent in Malpractice Cases
Authors: William J. Curran
Journal: New England Journal of Medicine (1986)

FOR at least two decades, American law in the malpractice field has often imposed unrealistic burdens on physicians in regard to informed consent.1 The courts have, in my opinion, turned the proper ethical obligation of a physician into an expansive intellectual exercise that is of dubious benefit to sick and worried patients. In an angry essay some years ago, Franz Ingelfinger referred to the legal rules as creating informed, but uneducated, consent.2 Perhaps worse is the fact that the doctrine of informed consent in its most severe form — which requires a physician to inform the patient of all potential . . .
PMO-106 The role of endoscopic ultrasound in identifying chronic pancreatitis: a comparison pathological specimens
Authors: L M Quinn, M Johnstone, R Sutton, S Sarkar
Journal: Gut (2012)

<h3>Introduction</h3> Imaging diagnostic criteria for chronic pancreatitis (CP) have long been debated. Patients with CP frequently undergo Endoscopic Ultrasound (EUS) as part of their diagnostic pathway, but it is unclear if should it be used as an adjunct for diagnosis or to simply exclude more sinister pathology. <h3>Aim</h3> To assess the effectiveness of EUS in diagnosis in patients with CP when comparing resection specimens as the gold standard. <h3>Methods</h3> All patients who had undergone EUS within 1 year prior to pancreatic resection between 2008 and 2011 at the Royal Liverpool University Hospital were identified from a prospectively maintained database. Resection specimens were compared to EUS and fine needle aspiration (FNA) findings. Agreement was assess using κ statistic and groups were compared using χ<sup>2</sup>. <h3>Results</h3> In the cohort of 93 patients (42% male; median [IQR] age 60 [51–72]) that underwent pancreatic resection, 60 (65%) patients had a clinical suspicion of CP. In the resection specimens CP was determined in 47 (51%) cases; 29 of which had CP alone and 18 with associated neoplasia. EUS correctly reported CP in 28 (60%) patients; 15 alone &amp; 13 with a mass or cyst. EUS falsely identified three as CP, and missed the diagnosis in 19 thus giving a sensitivity of 60% and specificity of 93% (positive predictive value 90%; negative predictive value 70%). Overall agreement EUS and resection histology was moderate (κ 0.53). In the 29 resection specimens where CP was the sole histological diagnosis, there was good agreement with EUS which identified this as the sole pathology in 18 (62%) cases (κ 0.62). However, in these cases, EUS reported CP in association with other pathology incorrectly in 11/29 (38%) of cases, querying neoplasia in 9/29(31%). The sensitivities of radial EUS (50) &amp; linear EUS with FNA (43) were similar (54% &amp; 65%; p=0.47). FNA cytology only confirmed the diagnosis of CP in 2/11(15%) were CP was the sole diagnosis, both of which were already been identified on sonography. The EUS detection of neoplasia in patients with CP was only 53% (9/17). <h3>Conclusion</h3> Overall EUS only showed moderate agreement with histology in diagnosing CP, which improved when CP was the sole diagnosis. There was no difference between linear and radial EUS, and FNA did not enhance the diagnosis of CP. This study shows that in context of CP, the EUS diagnosis of a concurrent neoplasia remains to prove difficult. Further detailed evaluation between clinical course, histological and EUS findings may be helpful. <h3>Competing interests</h3> None declared.
A therapeutically targetable mechanism of BCR-ABL–independent imatinib resistance in chronic myeloid leukemia
Authors: Leyuan Ma, Yi Shan, Robert Bai, Liting Xue, Christopher A. Eide, Jianhong Ou, Lihua J. Zhu, Lloyd Hutchinson, Jan Cerny, Hanna Jean Khoury, Zhi Sheng, Brian J. Druker, Shaoguang Li, Michael R. Green
Journal: Science Translational Medicine (2014)

A large-scale RNA interference screen reveals a new mechanism of imatinib resistance in chronic myeloid leukemia that can be therapeutically targeted.
Oral Antidiabetes Medication Adherence and Health Care Utilization Among Medicaid-Enrolled Type 2 Diabetic Patients Beginning Monotherapy
Authors: Rahul A. Shenolikar, Rajesh Balkrishnan
Journal: Diabetes Care (2008)

We recently conducted a study that examined the associations among medication adherence and health care costs and utilization in diabetic patients. Previous studies that have investigated these relationships did not necessarily examine patients undergoing antidiabetes therapy for the first time (1,2). We included patients who initiated oral monotherapy and continued with the same medication, as the majority of patients begin monotherapy.

The North Carolina Medicaid database was used to identify type 2 diabetic patients aged ≥18 years using at least one ICD-9 code (250.xx, excluding type 1 diabetes codes) and one National Drug Code for antidiabetes medication. Recipients aged ≥65 years …
The future of gambling in the United Kingdom
Authors: R. A Volberg
Journal: BMJ (2000)

For most people gambling is an enjoyable, if occasional, experience. For a minority, however, gambling leads to debilitating problems that harm the people close to them and the wider community. Problem gambling includes a range of behaviours that compromise, disrupt, or damage an individual's personal, family, or vocational pursuits, and, in its most severe forms, it has been recognised as a psychiatric disorder.1 A recent meta-analysis found that between 1% and 2% of adults aged 18 and over in the United States and Canada are pathological gamblers and an additional 2% to 4% of adults were classed as problem gamblers.2 Prevalence rates in Australia and New Zealand are similar.3 4 Problem gamblers and pathological gamblers are more likely than others in the general population to have been divorced, had physical and psychological problems, lost a job, been on welfare, been declared bankrupt, and been imprisoned.5

The availability …
Lung Cancer in Shipyard Workers
Authors: Ernst L. Wynder
Journal: New England Journal of Medicine (1978)

Decades ago it was established that risk of lung cancer was causatively associated not only with the independent use of tobacco products but also with the possible synergistic effect of cigarette smoking and exposure to certain industrial factors. The paper by Blot and his co-workers in the current issue of the Journal presents additional evidence for such an effect of cigarette smoking and asbestos exposure, or some other industrial carcinogen to which former shipyard workers in Georgia were exposed. This study appears to provide a partial explanation for the relatively high rate of lung cancer reported in the coastal region . . .
Surgery of the Adrenal Gland
Authors: Richard H. Egdahl
Journal: New England Journal of Medicine (1968)

THE purpose of this article is to present an overview of the adrenal gland from the surgeon's standpoint, with an emphasis on diagnosis and treatment. There will be no attempt to review completely the literature on each subject to be discussed, but rather a selective critique of available information will be made. Most of the papers to be discussed have been published during the last few years. Each of the most common conditions in which adrenal surgery is carried out will be discussed separately because the surgical approach varies considerably depending upon the type of abnormality present. More space is . . .
The effect of ethanol on asialoglycoprotein receptor–mediated phagocytosis of apoptotic cells by rat hepatocytes
Authors: B McVicker
Journal: Hepatology (2002)

Apoptotic cell death is a well-defined process that is controlled by intrinsic cellular mechanisms followed by the generation of apoptotic bodies and their subsequent rapid elimination through the action of phagocytic cells. Within the liver, the asialoglycoprotein receptor (ASGP-R) has been shown to be involved in the phagocytosis of apoptotic hepatocytes, as well as altered cellular endocytic events after ethanol administration. The goal of the present study was to further clarify the capacity of ASGP-R to phagocytose apoptotic cells in relationship to the damaging events that occur with alcohol consumption. For these experiments, we used an in vitro suspension assay coupled with flow cytometry to measure apoptotic cell engulfment by rat hepatocytes after chronic ethanol administration. The results of this assay indicated that the phagocytosis of apoptotic cells was decreased significantly (30% to 42%, P <.05) in the presence of antibody specific for ASGP-R as well as the introduction of competing sugars in the media. In addition, uptake of apoptotic cells was impaired by 40% to 60% (P <.05) in cells obtained from ethanol-fed animals as compared with controls. In conclusion, the ASGP-R is involved in the recognition and uptake of apoptotic cells and this process is altered significantly by ethanol treatment. These findings may play a role in a better understanding of the clinical manifestations of alcohol-induced liver injury as altered uptake of apoptotic cells via ASGP-R may result in the release of proinflammatory mediators, the introduction of autoimmune responses, and inflammatory injury to the tissue.
Reporting the Aspirin Study
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1988)

On January 28 of this year, the Journal published the preliminary results of the Physicians' Health Study, a double-blinded, placebo-controlled trial of aspirin for the primary prevention of myocardial infarction in 22,000 apparently healthy male physicians with no known contraindications to taking aspirin.1 One tablet of buffered aspirin every other day was found to have reduced the incidence of myocardial infarction in this group by 47 percent over a period of nearly five years.In the flurry of public excitement surrounding this trial, the Journal's handling of the report has been sharply criticized. We have been accused by some . . .
Insufficient Cholecystectomy Diagnosed by Endoscopic Ultrasonography
Authors: H. Hassan, P. Vilmann
Journal: Endoscopy (2004)

Recurrent attacks of upper right quadrant pain after cholecystectomy are not infrequent. In most of these cases, the cause of the pain remains undiagnosed. Insufficient cholecystectomy has been described as a rare cause of post-cholecystectomy pain, although the true incidence is unknown. It is difficult to diagnose a residual gallbladder or a large cystic duct with residual stones, due to the size of the remaining structures. This report presents three patients who had experienced a long period of agonizing biliary-type pain after cholecystectomy. Abdominal ultrasound examinations, and magnetic resonance cholangiopancreatography (MRCP) in one patient, were normal. Endoscopic ultrasonography (EUS) demonstrated the presence of a small cystic structure with echogenic foci compatible with a residual gallbladder containing small gallstones. Two of the three diagnoses were confirmed by repeat surgery. EUS thus appears to be a valuable method for diagnosing insufficient cholecystectomy, and should be considered in patients with persistent pain attacks after cholecystectomy.
Activin A and hepatocyte growth regulation
Authors: Raymond N. Dubois
Journal: Hepatology (1994)

The present study was conducted to examine the effect of activin A on growth of rat hepatocytes. EGF induced a 10-fold increase in DNA synthesis as assessed by [ 3 H]thymidine incorporation in cultured hepatocytes. When activin A was added together with EGF, DNA synthesis induced by EGF was markedly inhibited. Inhibition was detected at a concentration of 10 −10 M, and 5×10 −9 M activin A almost completely blocked EGF-mediated DNA synthesis. Similarly, activin A completely blocked DNA synthesis induced by hepatocyte growth factor/scatter factor. Activin A was capable of inhibiting EGF-mediated DNA synthesis, even when added 36 h after the addition of EGF. With the same time interval, TGF-β also blocked EGF-induced DNA synthesis. Although both activin A and TGF-β inhibited growth of hepatocytes in a similar manner, either activin A or TGF-β did not compete with each other in their binding when assessed by competitive binding using an iodinated ligand. When hepatocytes were incubated with EGF, release of bioactivity of activin A into culture medium was detected after 48 h or later. Activity of activin A was released from parenchymal cells but not from non-parenchymal cells. mRNA for β A subunit of activin was detected only slightly in unstimulated hepatocytes, but markedly increased at 48 h after the addition of EGF. To determine whether endogenously produced activin A affects DNA synthesis, we examined the effect of follistatin, an activin-binding protein that blocks the action of activin A. An addition of follistatin significantly enhanced EGF-induced DNA synthesis. Finally, in partial hepatectomized rat, expression of mRNA for β A subunit in liver was markedly increased 24 h after the partial hepatectomy. These results indicate that activin A inhibits initiation of DNA synthesis in hepatocytes by acting on its own receptor and that activin A acts as an autocrine inhibitor of DNA synthesis in rat hepatocytes.
Retinopathy Predicts Future Cardiovascular Events Among Type 2 Diabetic Patients: The Valpolicella Heart Diabetes Study
Authors: G. Targher
Journal: Diabetes Care (2006)

We read with interest the recent article by van Hecke et al. (1) showing that diabetic retinopathy is associated with an increased risk of mortality and cardiovascular disease (CVD) incidence among type 1 diabetic patients.

Because the available data on associations between retinopathy and incident CVD in large population samples of type 2 diabetic patients are limited and conflicting (2–4), we would like to offer recent findings from our large observational study. We carried out a prospective, nested, case-control study in 2,103 …
Hepatic dopamine sulfotransferases in untreated rats and in rats subjected to endocrine or hypertension-related treatments
Authors: Sanford S. Singer, Mark R. Palmert, Michael D. Redman, Diane M. Leahy, Theresa C. Feeser, Mark J. Lucarelli, Linda S. Volkwein, Margie Bruns
Journal: Hepatology (1988)

Here we describe the dopamine sulfotransferase activity of rat liver cytosol. With cytosol, 3′-phosphoadeno-sine-5′-phosphosulfate and dopamine K m values were 17.2 ± 4.1 and 22.4 ± 3.5 μ M . Females possessed 23 to 37% of dopamine sulfotransferase levels, per gm liver, in males. DEAE-Sephadex A-50 chromatography resolved dopamine sulfotransferase activity to dopamine sulfotransferase I and dopamine sulfotransferase II. Dopamine sulfotransferase II comprised 79 ± 10 or 61 ± 18% of dopamine sulfotransferase in males or females in routine assays. 4-Methoxytyramine gave 609 or 179% of mean dopamine sulfotransferase activity with dopamine sulfotransferase I or II. Dopamine and 3-methoxytyramine were comparable substrates. Epinephrine was less effective. Mn ++ , Cd ++ , Zn ++ , Na + and K + inhibited dopamine sulfotransferase II. Mg ++ activated it. Dopamine sulfotransferase II from males was purified 184 ± 64-fold. Its K m values for 3′-phosphoad-enosine-5′-phosphosulfate and dopamine were 12.7 ± 1.5 and 47.5 ± 6.7 μ M , respectively. Its dopamine sulfotransferase mechanism was sequential. The molecular weight of dopamine sulfotransferase II was 49,100 ± 4,000 by Sephadex G-100 chromatography. Dopamine sulfotransferase II preferred phenol to catecholamines. Dopamine and 3,4-dihydroxybenzylamine were its best catecholamine substrates. Adrenalectomy or castration of males led to 35 or 45% mean decreases of dopamine sulfotransferase levels, indicating adrenal and gonadal participation in control of dopamine sulfotransferase production. Testosterone had no effect in either sex, whereas estradiol led to 40% mean decreases of dopamine sulfotransferase levels in males. This suggested a role for ovaries in dopamine sulfotransferase production, supported by 55 to 102% increased dopamine sulfotransferase levels after ovariectomy. Okamoto-hypertensive males or males given hypertensogenic doses of cortisol exhibited 37 or 48% mean increases of dopamine sulfotransferase levels per gm liver. Antihypertensive spironolactone or hydralazine led to 30% mean decreases of dopamine sulfotransferase levels. Altered dopamine sulfotransferase levels after all experimental manipulations were due mostly to changed dopamine sulfotransferase II content. Dopamine sulfotransferase II is compared to other reported enzymes that sulfate catecholamines.
Guidelines on treating risk factors turn healthy people into patients, doctors say
Authors: Bryan Christie
Journal: BMJ (2006)

Medicine may be going too far in extending risk thresholds for cardiovascular disease—turning many healthy people into worried patients, warned doctors at a conference in Edinburgh last week. 

The conference, organised by the Royal College of Physicians of Edinburgh, expressed concern at recent international and UK guidelines that widen the range of people to be targeted for treatment with blood pressure and cholesterol lowering drugs. 

Paul Padfield, a consultant physician in Edinburgh and one of the conference's organisers, said this risks medicalising states previously considered normal while putting more pressure on NHS budgets. …
Severe cholestasis leads to vitamin D depletion without perturbing its C-25 hydroxylation in the dog
Authors: Victor Plourde, Marielle Gascon-Barré, Bernard Willems, P.-Michel Huet
Journal: Hepatology (1988)

The role of the liver as a contributory factor in the vitamin D deficiency of cholestatic liver disease has been studied in vivo in dogs with chronic bile duct ligation, whereas controls underwent diversion of the bile flow through the urinary bladder via a choledococystostomy anastomosis. The hepatic extraction of vitamin D3 was evaluated by the multiple indicator dilution technique, and the formation of 25-hydroxyvitamin D3 was assessed by directly sampling the hepatic effluent for up to 150 min after vitamin D3 administration. The serum and hemodynamic data indicate that dogs with chronic bile duct ligation had severe cholestasis and hepatocel-lular injury; histologically, macronodular cirrhosis was present. Dogs with choledococystostomy anastomosis had normal livers and normal liver function. The data indicate that the absence of normal bile flow into the intestinal lumen led to a progressive depletion of vitamin D reserve in both animals with choledococystostomy anastomosis and those with chronic bile duct ligation. However, neither the hepatic fractional extraction of vitamin D3, its hepatic clearance nor its transformation into 25-hydroxyvitamin D3 was significantly changed by chronic bile duct ligation. The results of the present studies indicate that the hepatic handling of vitamin D3 including its C-25 hydroxylation, is well preserved in the presence of severe cholestasis. They also suggest that the state of vitamin D depletion which often accompanies chronic cholestatic liver disease can largely be accounted for by factors such as secondary malabsorption of the vitamin due to the absence of adequate amounts of bile salts in the intestinal lumen, or by other factors which seem independent of the hepatic metabolism of vitamin D.