tbuckley/cabot-search huggingface dataset:
In search of abnormal enzyme activities of hepatic cholesterol metabolism in patients with cholesterol gallstone disease
Authors: Attilio Rigotti, Flavio Nervi
Journal: Hepatology (1991)

Hepatic cholesterol metabolism was examined in 27 Swedish patients with cholesterol gallstone disease and in 13 patients free of gallstones operated for roentgenographically suspect polyps in the gallbladder. All 40 patients underwent cholecystectomy, and a liver biopsy and gallbladder bile were obtained at surgery. The cholesterol saturation of gallbladder bile was significantly higher in patients with gallstones compared to the gallstone-free controls (131 ± 13 vs. 75 ± 5%, P &lt; 0.001). Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 ± 11 vs. and 109 ± 22 pmol/min per mg protein, respectively). The activity of cholesterol 7 α-hydroxylase, catalyzing the catabolism of cholesterol to bile acids, was not significantly decreased in gallstone patients (6.2 ± 1.1 vs. 8.0 ± 2.0 pmol/min per mg protein). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme A: cholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 ± 0.4 vs. 6.7 ± 1.1 pmol/min per mg protein). In the presence of exogenous cholesterol, ACAT activity increased by more than fourfold in both groups. No correlation was found between the saturation of gallbladder bile and any of the mentioned enzyme activities in gallstone patients. It is concluded that distinct abnormalities in cholesterol metabolizing enzymes are not of major importance for development of gallstones in Swedish patients with cholesterol gallstone disease. The results support the contention that the etiology of cholesterol gallstones is multifactorial.
Canadian MPs dismiss findings that food policies are leading to hunger and obesity
Authors: B. Kermode-Scott
Journal: BMJ (2012)

Members of Canada’s cabinet have engaged in a war of words with the United Nations’ special rapporteur on the right to food, who accused the government of widening inequalities in society and failing to tackle hunger and poor diet.

The special rapporteur, Olivier De Schutter, a professor at the Catholic University of Louvain in Belgium, who was in Canada from 6 to 16 May, chastised the government in a press statement for having “a system that presents barriers for the poor to access nutritious diets and that tolerates increased inequalities between rich and poor, and Aboriginal and non-Aboriginal peoples.”1

He pointed out that a growing number of people across Canada remain unable to meet …
Clinical Application of a Simple Qualitative Serum Acetone Test in Diabetes Mellitus
Authors: Otto C. Page
Journal: New England Journal of Medicine (1953)

SIMPLE methods for the qualitative and roughly quantitative determination of serum acetone have been known for some time.1 Duncan,2 , 3 particularly, has pointed out the value of these simple tests in the early diagnosis and treatment of diabetic acidosis. Perhaps because of their very simplicity, the tests have failed to gain the wide recognition they deserve. A limited experience with one of these simple tests is herewith reported in the hope that others may be encouraged to use it in situations in which more elaborate determinations are unavailable.MethodBecause of its convenience the nitroprusside method has been found to serve . . .
Radiofrequency ablation and endoscopic resection in a single session for Barrett’s esophagus containing early neoplasia: a feasibility study
Authors: F. van Vilsteren, L. Alvarez Herrero, R. Pouw, M. Visser, F. ten Kate, M. van Berge Henegouwen, E. Schoon, B. Weusten, J. Bergman
Journal: Endoscopy (2012)

Endoscopic resection with radiofrequency ablation (RFA) 6 weeks later safely and effectively eradicates Barrett's esophagus with high grade dysplasia (HGD) and early cancer. After widespread endoscopic resection, related scarring may hamper balloon-based circumferential RFA (c-RFA). However c-RFA immediately followed by endoscopic resection in the same session might avoid the impact of scarring and reduce laceration and stenosis risk. We aimed to assess the feasibility of such an approach.Patients with Barrett's esophagus ≥ 3 cm and ≥ 1 visible lesion (HGD/early cancer) were included. Visible lesions were marked with cautery, and c-RFA (12 J/cm2) was delivered using two applications and a cleaning step, followed by resection of the delineated area. Outcome measures were surface regression of Barrett's esophagus at 3 months, need for subsequent c-RFA, complications, and quality of resection specimens.24 patients (20 men, 4 women; mean age 68 years, standard deviation [SD] 12; Barrett's esophagus median length C6M8) underwent single-session c-RFA + endoscopic resection, providing a median of 4 (interquartile range [IQR] 2 - 6) resection specimens (early cancer 18 patients; HGD 6). Complications included 1 perforation, 4 bleedings, and 5 stenoses; all were managed endoscopically. Specimens allowed assessment of neoplasia depth, differentiation, and lymphatic/vascular invasion. Median Barrett's esophagus surface regression at 3 months was 95 %. No patient required a second c-RFA procedure and 40 % required repeat endoscopic resection for visible lesions. Complete response for neoplasia was achieved in 100 % and complete response for intestinal metaplasia (CR-IM) in 95 %.c-RFA followed by endoscopic resection in the same session is feasible, but technically demanding and associated with a substantial rate of complications and repeat endoscopic resection. This approach should be reserved for selected cases in expert centers, with endoscopic resection and RFA 6 - 8 weeks later remaining the standard combined approach.
Intensive vascular training in stage IIb of peripheral arterial occlusive disease. The additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training.
Authors: P Scheffler, D de la Hamette, J Gross, H Mueller, H Schieffer
Journal: Circulation (1994)

In a randomized open study, the combination of either prostaglandin E1 (PGE1) or pentoxifylline with controlled vascular training was compared with vascular training alone in patients with peripheral arterial occlusive disease in stage IIb. Forty-four patients were randomly assigned to treatment either of intensive vascular training alone (n = 15) or in combination with either i.v. pentoxifylline (200 mg over 2 hours BID, n = 15) or PGE1 (40 micrograms over 2 hours BID, n = 14). The basic therapy was a well-defined routine for vascular training, which was identical for all groups. The duration of therapy was 4 weeks. In all three test groups, there was a significant increase in the walking distance. There was a 119% increase in symptom-free walking distance in the exercise-only group. In comparison with exercise alone, the additional administration of pentoxifylline produced no greater effect; the increase was 105%. In contrast, administration of PGE1 combined with exercise achieved a remarkable improvement of 604%. Between-group comparison revealed the significant superiority of treatment with PGE1 (P &lt; .05). During the 1-year follow-up, there was a reduction in the walking performance in all groups, albeit of variable extent. In the exercise-only and the pentoxifylline groups, the maintained increase in walking distance was only 30% compared with baseline values before the beginning of therapy. In the PGE1 group, on the other hand, the maintained improvement was 149%. Nine of 14 patients were still in stage IIa of peripheral arterial occlusive disease 1 year after PGE1 therapy.
General Practitioners' Expenses
Authors: J. F. Robinson
Journal: BMJ (1964)

published our statistics and reports for all to see.My own practice visits have been reduced by 50% over the past 10 years.Amongst four doctors at this centre one colleague still has twice the visiting rate of the others, and that in practices with almost identical age and sex distribution and incidence of morbidity.How can one explain these differences, except on the basis of personal habit ?In Sweden, which has the lowest morbidity rate in the world, daily visiting is only about one-quarter the rate in this country.Since the population of these islands is increasing at a faster rate than the output of doctors within the next decade it is even more important and urgent that family doctors should use their efforts efficiently, and the population use the practitioners' time judiciously.-Iam, etc., Manchester 13. H. W. ASHWORTH.Poor Rate for the Job SIR,-Having recently received-three months in arrears-our annual cheque for ser- vices rendered at the local cottage hospital, our attention has been focused on the low level at which these services are rewarded.We staff, exclusively, this 14-bed hospital and are on call permanently for all emergen- cies and casualties.Minor surgery and fracture treatment are performed regularly and many x-ray films are seen and interpreted.The total reward for six senior, well- qualified practitioners, including an M.R.C.P., is £250, most probably less than the income of any single member of the domestic staff.We have conveyed news of this disgraceful rate for the job to our local medical com- mittee and have expressed our sentiments to the hospital management committee and regional board and hope that others simi- larly rewarded for their professional labours will likewise agitate.-Weare, etc.,
Acute kidney injury is a more important safety issue than MRSA, says NICE
Authors: N. Hawkes
Journal: BMJ (2013)

Thousands of lives could be saved by better prevention, detection, and treatment of acute kidney injury in England, says a new guideline from the National Institute for Health and Care Excellence (NICE), summarised in the BMJ .1 2

Though common—occurring in 13-18% of all people admitted to hospital—acute kidney injury falls between the gaps in medical specialties and may go undetected. Patients admitted with an acute condition are treated for that condition but do not always see a nephrologist.

In 2009 the National Confidential Enquiry into Patient Outcome and Death found that only half of patients who had died from acute kidney injury had received good care.3 4 This report led to a request to NICE from the Department of Health for …
Applicability of dermoscopy for evaluation of patients' response to nonablative therapies for the treatment of superficial basal cell carcinoma
Authors: Z. Apalla, A. Lallas, T. Tzellos, T. Sidiropoulos, I. Lefaki, M. Trakatelli, E. Sotiriou, E. Lazaridou, G. Evangelou, A. Patsatsi, A. Kyrgidis, A. Stratigos, I. Zalaudek, G. Argenziano, D. Ioannides
Journal: British Journal of Dermatology (2013)

Applicability of dermoscopy in evaluation of outcome and monitoring of superficial basal cell carcinoma (sBCC) after nonablative therapies has not been sufficiently assessed.Certain dermoscopic criteria, namely pigmented structures, ulceration and arborizing vessels, have been suggested to predict the presence of residual disease [residual disease-associated dermoscopic criteria (RDADC)]. We aimed to assess this hypothesis.Lesions exhibiting RDADC 3 months after treatment were biopsied and in the case of histopathological confirmation were excised. Lesions characterized by white/red structureless areas, superficial fine telangiectasias, or lacking any dermoscopic criterion, were monitored for 12 months.At the 3-month evaluation, one or more of the RDADC were detected in 25/98 (25·5%) sBCCs, in which histology confirmed tumour persistence. In 45 (61·6%) of the 73 remaining lesions, dermoscopy showed white/red structureless areas and/or superficial fine telangiectasias. Twenty-eight lacked any dermoscopic criterion of sBCC. The two latter groups entered follow-up. In total, disease recurred in 13 (17·8%) of the 73 lesions.RDADC accurately predict residual disease. Absence of dermoscopic criteria of sBCC safely predicts complete histopathological clearance. Detection of white/red structureless areas and/or superficial fine telangiectasias warrants close monitoring to recognize early recurrence.
Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans.
Authors: C von Schacky, S Fischer, P C Weber
Journal: Journal of Clinical Investigation (1985)

We studied the incorporation and metabolism of eicosapentanoic (EPA) and docosahexaenoic acid in six human volunteers who supplemented their normal Western diet for 5 mo daily with 10-40 ml of cod liver oil, rich in omega-3 polyunsaturated fatty acids. EPA and docosahexaenoic acid were incorporated into the total phospholipids of plasma, platelets, and erythrocytes in a dose- and time-dependent manner. During omega-3 fatty acid ingestion serum triacylglycerols were lowered and platelet aggregation upon low doses of collagen was reduced. Concomitantly, formation and excretion of prostanoids showed a characteristic change. As measured in serum from whole clotted blood, thromboxane A3 was formed in small amounts, whereas thromboxane A2 formation was reduced to 50% of control values. Excretion of the main urinary thromboxane A metabolites was unaltered in subjects with low basal excretion rates, but decreased markedly in two subjects with high control values. As determined from the main urinary metabolite, prostaglandin I3 was formed from EPA at rates up to 50% of unaltered prostaglandin I2 formation. The biochemical and functional changes observed lasted for the entire supplementation period of 5 mo and were reversible within 12 wk after cessation of cod liver oil intake. Favorable changes induced by long-chain omega-3 fatty acids include a dose-related and sustained shift of the prostaglandin I/thromboxane A balance to a more antiaggregatory and vasodilatory state.
Effects of lysophosphatidylcholine on electrophysiological properties and excitation-contraction coupling in isolated guinea pig ventricular myocytes.
Authors: E Liu, J I Goldhaber, J N Weiss
Journal: Journal of Clinical Investigation (1991)

Lysophosphoglyceride accumulation in ischemic myocardium has been implicated as a cause of arrhythmias. We examined the effects of lysophosphatidylcholine (LPC) in isolated guinea pig ventricular myocytes. In paced myocytes loaded with the Ca2+ indicator Indo-1-AM and studied at room temperature, 20 microM LPC caused an initial positive inotropic effect followed by spontaneous automaticity, a decline in active cell shortening, and progressive diastolic shortening (contracture) leading to cell death. These changes were accompanied by a progressive increase in cytosolic [Ca2+]i. In patch-clamped myocytes dialyzed internally with high EGTA concentrations, LPC caused membrane depolarization, shortening of the action potential duration, and abnormal automaticity as seen in multicellular preparations. Voltage clamp experiments revealed the appearance of a nonselective leak conductance without significant changes in the delayed rectifier K+ current, inward rectifier K+ current, L-type Ca2+ current, and T-type Ca2+ current. Pretreatment with 20 mM caffeine and [Ca2+]o-free solution did not prevent the leak current. In patch clamped myocytes loaded with 0.1 mM Fura-2 salt, the [Ca2+]i transient induced by either voltage clamps or brief caffeine exposure remained normal until the nonselective leak current developed. The Na(+)-Ca2+ exchange current elicited during caffeine-induced [Ca2+]i transients also did not appear to be altered by LPC. Qualitatively similar results were obtained in myocytes studied at 35 degrees C. The membrane detergent saponin (0.005% wt/wt) mimicked all of the effects of LPC. We conclude that under these experimental conditions the effects of LPC are most compatible with a detergent action causing membrane leakiness with resultant depolarization, [Ca2+]i overload, and contracture.
Beneficial effects of pulsatile perfusion in the hypertrophied ventricle during ventricular fibrillation.
Authors: T J Bixler, P G Magee, J T Flaherty, T J Gardner, V L Gott
Journal: Circulation (1979)

To assess the potential benefit of pulsatile perfusion inthe hypertrophied heart during fibrillation, 10 dogs with left ventricular hypertrophy, produced by previous supravalvular aortic banding, were used to compare linear and pulsatile perfusion in the fibrillating heart during total cardiopulmonary bypass. The mass spectrometer was used to measure subendocardial PCO2 and PO2 (PmCO2 and PmO2), and radioactive microspheres were utilized to measure myocardial blood flow in the same layers. Pulsatile perfusion was established using the recently develop "bubble tubing," which produces a pulse pressure of at least 20 mm Hg and can be used in a standard roller-pump apparatus. Both linear and pulsatile flows were compared at mean aortic root pressures of 80 and 50 mm Hg, and these four combinations of aortic root pressure and type of flow were employed for periods of 30 minutes each. Myocardial ischemia developed during linear coronary perfusion at 50 mm Hg, as evidenced by an elevation of PmCO2. Ischemia was not evident during pulsatile perfusion at the same mean pressure. Reversal ischemia was a result of increased myocardial blood flow and pulsatile perfusion, and this increase was shown to occur maximally in the deeper subendocardial layer. Ischemia was not eviden during linear or pulsatile perfusion at an mean perfusion pressure 80 mm Hg. Thus, if lower perfusion pressures are to be tolerated in patients with left ventricular hypertrophy, pulsatile perfusion with the bubble tubing technique may prevent the development of subendocardial ischemia or infarction.
Ascites With a Communicating Hydrocele Detected by Peritoneal Scintigraphy
Authors: Chien-Chin Hsu, Yu-Wen Chen, Ya-Wen Chuang, Ying-Fong Huang
Journal: Clinical Nuclear Medicine (2004)

A hydrocele is a collection of fluid within the tunica or processus vaginalis. Most pediatric hydroceles are congenital and adult hydroceles are usually secondary. The latter can present acutely from local injury, infection, radiotherapy, or increased intraabdominal pressure. A 53-year-old man with underlying liver cirrhosis was admitted for dyspnea and abdominal distention. Massive ascites with swelling of the right hemiscrotum was noted. A communicating hydrocele was detected by peritoneal scintigraphy. After surgical repair of the communicating shunt by a Bassini procedure, the problem of the right hydrocele was resolved.
TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer
Authors: Saradiya Chatterjee, Lucile Crozet, Diane Damotte, Kristina Iribarren, Catherine Schramm, Marco Alifano, Audrey Lupo, Julien Cherfils-Vicini, Jeremy Goc, Sandrine Katsahian, Mohammad Younes, Marie Caroline Dieu-Nosjean, Wolf Herman Fridman, Catherine Sautès-Fridman, Isabelle Cremer
Journal: Cancer Research (2014)

Toll-like receptors (TLR) recognize pathogen molecules and danger-associated signals that stimulate inflammatory processes. TLRs have been studied mainly in antigen-presenting cells, where they exert important immune regulatory functions, but they are also expressed by epithelial tumor cells, where they have been implicated in tumor progression. In this study, we demonstrate that the injection of TLR7 agonist in NOD/SCID mice, in C57BL/6 wild-type, and TLR7-deficient mice grafted with lung adenocarcinoma tumor cells leads to increased tumor progression and chemotherapeutic resistance. In patients with non-small cell lung cancer, expression analyses revealed that high TLR7 expression was strongly associated with resistance to neoadjuvant chemotherapy and poor clinical outcomes. Our findings delineate a crucial role for TLR7 in lung cancer physiopathology. Cancer Res; 74(18); 5008-18. ©2014 AACR.
Abstract 4684: Autophagy blockade sensitizes prostate cancer cells towards Src family kinase inhibitors
Authors: Zhaoju Wu, Pei-Ching Chang, Joy C. Yang, Cheng-Ying Chu, Ling-Yu Wang, Nien-Tsu Chen, Ai-Hong Ma, Sonal J. Desai, Su Hao Lo, Christopher P. Evans, Kit S. Lam, Hsing-Jien Kung
Journal: Cancer Research (2010)

Abstract There is overwhelming evidence that tyrosine kinases play an important role in cancer development. As a prototype of targeted therapy, tyrosine kinase inhibitors are now successfully applied to cancer treatment. However, as single agents, tyrosine kinase inhibitors have not achieved satisfactory results in the treatment of prostate cancer, principally due to their inability to efficiently kill tumor cells. Our lab has been interested in the role of the Src complex in prostate cancer progression including the induction of androgen independence and metastasis. Previously, we reported that Src inhibitors such as saracatinib and PP2 caused G1 growth arrest and diminished invasiveness in prostate cancer cells, but rarely apoptosis. Here, we have shown that Src family kinase (SFK) inhibitors can induce a high level of autophagy, which protects treated cells from undergoing apoptosis. Src siRNA knockdown experiments confirmed that autophagy was indeed caused by the lack of Src activity. The SFK inhibitor-induced autophagy is accompanied by the inhibition of PI3K (type I)/Akt/mTOR signaling pathway. To test whether autophagy blockade could lead to enhanced cell death, pharmacological inhibitors (3-methyladenine and chloroquine) and a genetic inhibitor (siRNA targeting Atg7) were used in combination with SFK inhibitors. The results showed that autophagy inhibition effectively enhanced cell killing induced by SFK inhibitors. Importantly, we showed a combination of saracatinib with chloroquine in mice significantly reduced prostate cancer (PC3) xenograft growth, compared with the control group. Taken together, these data suggest that 1) autophagy serves a protective role in SFK inhibitor-mediated cell killing; 2) clinically acceptable autophagy modulators may be used beneficially as adjunctive therapeutic agents for SFK inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4684.
Role of Phospholipase A<sub>2</sub> Activation in Histamine Release from Human Basophils
Authors: Yutaka Morita, Noriko Aida, Terumasa Miyamoto
Journal: Allergy (1983)

The present experiments were undertaken to investigate the role of phospholipase A 2 (PLA 2 ) activation in histamine release from human basophils. A PLA 2 inhibitor, P‐bromophenacyl bromide (BPB), inhibited IgE‐mediated anti‐IgE‐induced histamine release from human basophils with a concentration of drug required to produce 50% inhibition (IC 50 ) of 1.5 × 10 −6 m when leukocytes were preincubated with this agent for 15 min. Histamine release induced by calcium ionophore A23187 and formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine was also blocked by BPB with IC 50 of 4.1 × 10 −6 m, and 3.5 × 10 −6 m, respectively. A PLA 2 activator, 12–0‐tetradecanoylphorbol‐13‐acetate (TPA) caused basophil histamine release with a dose‐dependent fashion. BPB inhibited TPA‐induced histamine release (IC 50 : 2.5 × 10 −6 m). However, another PLA 2 activator, melittin, and PLA 2 did not release histamine through non‐cytotoxic mechanisms. Collectively, these results suggest that PLA 2 activation plays a central role in histamine release from human basophils via generation of lysophosphatidylcholine or products of the lipoxygenase pathway of arachidonic acid metabolism.