tbuckley/cabot-search huggingface dataset:
Substances Producing Pain and Itch
Authors: Philip C. Anderson
Journal: JAMA (1964)

Interest in the inflammatory reaction has been revived, in part, by the biochemical investigations of Spector, Margolis, and others. Now, in this well-written book the sensory aspects of inflammation and pain sensation in general are discussed from the physiologist's and pharmacologist's viewpoint. Assuming that the reader has no prior knowledge of algology, the authors furnish at the outset, through a moderately detailed review of their own investigations, the necessary definitions, common terms, abbreviations, and experimental techniques used in the study of pain-producing (algogenic) substances. Thereafter, the algogenic effect of salt solutions, acids, kinens, damaged tissues, serum proteins, and even the sting of the deadly stonefish seems understandable. Over 700 useful references are listed. The authors discuss thoroughly the role of Hageman factor in the release of kinens from human plasma, showing the relation of clotting mechanisms to the inflammatory reaction. Less is known about pruritus than about pain, perhaps because
Patients and staff not fully engaged with commissioning
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Neither patients nor frontline staff, such as GPs and primary care nurses, have had a strong influence on most patient and public engagement strategies, a survey has found. The Picker Institute, a research charity that promotes patient centred health care, which carried out the survey, says that its findings amount to the beginnings of a cultural change. It warns, however, that the change has so far penetrated only trusts’ own management.

More than eight in 10 primary care trusts say that they have made considerable changes in the past two years in the way that they organise patient and public engagement in commissioning.

The English government launched …
Belgium to tighten drug advertising laws
Authors: Rory Watson
Journal: BMJ (2006)

The Belgian government is drawing up legislation to strengthen existing controls on advertising drugs and cures for specific illnesses, after a high profile row broke out between a consumer organisation and a public health foundation.

It is illegal in Belgium to advertise drugs for which the costs are reimbursed by one of the social security system's insurers. The advertising of drugs that are not refundable is permitted, but a special committee must …
Abstract PD1-3: Ph1b study of the PI3K inhibitor GDC-0032 in combination with fulvestrant in patients with hormone receptor-positive advanced breast cancer
Authors: D Juric, C Saura, A Cervantes, C Kurkjian, MR Patel, J Sachdev, I Mayer, IE Krop, M Oliveira, S Sanabria, S Cheeti, RS Lin, RA Graham, TR Wilson, H Parmar, JY Hsu, DD Von Hoff, J Baselga
Journal: Cancer Research (2013)

Abstract Background: GDC-0032 is a next-generation PI3K inhibitor with increased anti-tumor activity against PIK3CA mutant cancers. GDC-0032 is an orally bioavailable, potent, and selective inhibitor of Class I PI3K alpha, delta, and gamma isoforms, with 30-fold less inhibition of the PI3K beta isoform relative to the PI3K alpha isoform. Preclinical data show that GDC-0032 has enhanced activity against PI3K alpha isoform (PIK3CA) mutant breast cancer cell lines. Preclinical data also show enhanced antitumor activity when GDC-0032 is combined with fulvestrant. Material and Methods: A Phase 1b dose escalation study was conducted with evaluation of GDC-0032 doses ranging from 6-9 mg QD in combination with fulvestrant 500mg q4wk (with loading dose of 500mg at day 1, 14 and 28) in a modified 3+3 design. A dose expansion cohort was conducted at the recommended Phase 2 dose of 6 mg QD. Safety and tolerability of GDC-0032 was assessed, as well as pharmacokinetics (PK), pharmacodynamic (PD) assessment of PI3K pathway inhibition by paired tumor biopsies and by FDG-PET, and anti-tumor activity by RECIST. Results: As of 1 Mar 2013, 17 patients were enrolled onto this study with the completion of dose escalation. No dose limiting toxicities (DLTs) were observed at either the 6 mg or 9 mg dose levels. Adverse events (AEs) assessed by the investigator as related to GDC-0032 in ≥10% of patients, were diarrhea, hyperglycemia, stomatitis, fatigue, asthenia, decreased appetite, nausea, mucosal inflammation and rash. No observed apparent PK interactions were observed between GDC-0032 and fulvestrant. The median number of prior systemic therapies was 6. Metabolic partial responses via FDG-PET (≥ 20% decrease in mSUVmax) were observed in 8 out of 11 patients assessed (73%). Confirmed partial responses by RECIST have been observed at both the 6mg and 9mg GDC-0032 dose levels. These include patients who have had prior treatment with fulvestrant. As of 29 May 2013, enrollment onto the dose escalation and expansion cohort has been completed (n = 27). Updated data on safety, pharmacodynamics, efficacy, and biomarker correlates will be presented. Conclusions: The combination of GDC-0032 and fulvestrant is a well-tolerated regimen with promising preliminary efficacy. GDC-0032 is being further investigated in combination with fulvestrant for patients with hormone receptor-positive advanced breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD1-3.
Adenosine triphosphate release by osmotic shock and hemoglobin A1C in diabetic subjects' erythrocytes
Authors: Enrico Petruzzi, Claudio Orlando, Pamela Pinzani, Roberta Sestini, Attilio Del Rosso, Germana Dini, Elisabetta Tanganelli, Antonio Buggiani, Mario Pazzagli
Journal: Metabolism (1994)
Focused liver ablation by cavitation in the rabbit: a potential new method of extracorporeal treatment.
Authors: F Prat, J Y Chapelon, F Abou el Fadil, A Sibille, Y Theilliere, T Ponchon, D Cathignol
Journal: Gut (1994)

A new device was used to achieve focused tissue ablation by shockwave induced cavitation. The device produced a half cycle of negative pressure followed by a shock wave, thus enhancing cavitation. Twenty eight New Zealand rabbits were treated. Therapeutic ultrasound was targeted at the centre of the liver under ultrasound guidance. The focal volume was scanned with a computer operated x-y-z micropositioner. The number and frequency of bursts as well as the distance between two x-y-z displacements were preselected. The relation of tissue ablation seen to preselected parameters, effects on surrounding tissues, biological side effects, and mode of healing were studied. Macroscopy, planimetry, and quantitative microscopy were used. Focused and homogeneous tissue ablation was achieved within well defined limits. Maximal tissue ablation was seen in the centre of the target. Liver surrounding the target remained unaffected. Lesions were made of a-cellular spots surrounded by disorganised rims of necrotic hepatocytes; 24 hours after treatment, the changes (mean (SEM)) in alanine transaminase and haemoglobin were +225 (36)% and -2.4 (2)% respectively. Serum transaminases, haemoglobinaemia, and packed cell volume were normal 21 days after treatment and the target area was replaced by a fibrous scar. It is concluded that ultrasound cavitation may achieve extracorporeal intrahepatic tissue ablation inside a predetermined target. This technique should now be tested in an animal hepatic tumour model.
Seasonal variation and time trends of deaths from asthma in England and Wales 1960-82.
Authors: A Khot, R Burn
Journal: BMJ (1984)

Monthly trends in deaths attributed to asthma in the 5-34 year age group were examined for England and Wales over the period 1960-82. Deaths were most frequent in the third quarter (July to September) and peaked in August. Analysis of the 1970-82 period showed that this variation was present in the three constituent age groups 5-14, 15-24, and 25-34 but was most pronounced in the 5-14 year olds.
Comparison of C-11 Methionine and C-11 Choline for PET Imaging of Brain Metastases
Authors: Christof Rottenburger, Michael Hentschel, Thomas Kelly, Michael Trippel, Ingo Brink, Thomas Reithmeier, Philipp Tobias Meyer, Guido Nikkhah
Journal: Clinical Nuclear Medicine (2011)

The aim of the study was the comparison of C-11 methionine (MET) and C-11 choline (CHO) in the positron emission tomography (PET) imaging of brain metastases in correlation to the histopathology findings in stereotactic biopsy.In all, 8 patients underwent MET and CHO PET and magnetic resonance imaging, in 7 of these, the metastases were previously treated by radiation therapy. Histopathologic diagnosis was made for each patient by frame-based stereotactic serial biopsy. Standardized uptake values of tumor uptake and lesion-to-normal brain tissue ratios (LNRs) of the lesions were determined. LNRs for each tracer were compared with the histopathology findings and follow-up.In 6 patients, biopsy revealed viable metastases, 1 patient suffered from tumor recurrence in follow-up and 1 patient was tumor free in biopsy and follow-up. In the last mentioned patient, LNR was the lowest determined in all patients for CHO, but not for MET. Mean standardized uptake values of the lesions were in median 1.8 for MET and 1.1 for CHO, median LNRs were 1.5 for MET and 6.6 for CHO. LNRs for CHO were significant higher than those for MET (P = 0.007).In the direct comparison to the well-established amino acid tracer MET, CHO seems to be promising for the imaging of brain metastases because of significantly higher LNRs in tumor tissue compared with MET without evidence for a lower specificity of CHO uptake.
Changes in Upper Airway Size during Tidal Breathing in Children with Obstructive Sleep Apnea Syndrome
Authors: Raanan Arens, Sanghun Sin, Joseph M. McDonough, John M. Palmer, Troy Dominguez, Heiko Meyer, David M. Wootton, Allan I. Pack
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.
Potential harms of type 2 diabetes drugs have been ignored, finds BMJ investigation
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Drug regulators and manufacturers have been criticised for failing to take enough action in response to research highlighting the potential serious adverse effects of new forms of drugs used to treat type 2 diabetes, known as glucagon-like peptide-1 (GLP-1) based drugs.

A joint investigation by the BMJ and Channel 4’s Dispatches current affairs programme has found that concerns about the drugs, also called incretin therapies, started to emerge in 2007.1 Since then many published reports, regulatory documents, and adverse event databases have highlighted concerns about the safety of these drugs and linked them with an increased risk of …
Full-Length Semaphorin-3C Is an Inhibitor of Tumor Lymphangiogenesis and Metastasis
Authors: Yelena Mumblat, Ofra Kessler, Neta Ilan, Gera Neufeld
Journal: Cancer Research (2015)

Semaphorins play important regulatory roles in diverse processes such as axon guidance, angiogenesis, and immune responses. We find that semaphorin-3C (sema3C) induces the collapse of the cytoskeleton of lymphatic endothelial cells (LEC) in a neuropilin-2-, plexin-D1-, and plexin-A1-dependent manner, while most other semaphorins, including antiangiogenic semaphorins such as sema3A do not. Sema3C is cleaved, like other class-3 semaphorins, by furin-like pro-protein convertases (FPPC). Cleaved sema3C (p65-Sema3C) was unable to induce the collapse of the cytoskeleton of LEC. FPPC are strongly upregulated in tumor cells. In order to examine the effects of full-length sema3C on tumor progression, we therefore generated an active point mutated furin cleavage-resistant sema3C (FR-sema3C). FR-sema3C inhibited potently proliferation of LEC and to a lesser extent proliferation of human umbilical vein-derived endothelial cells. FR-sema3C also inhibited VEGF-C-induced phosphorylation of VEGFR-3, ERK1/2, and AKT. Expression of recombinant FR-sema3C in metastatic, triple-negative LM2-4 breast cancer cells did not affect their migration or proliferation in vitro. However, tumors derived from FR-sema3C-expressing LM2-4 cells implanted in mammary fat pads developed at a slower rate, contained a lower concentration of blood vessels and lymph vessels, and metastasized much less effectively to lymph nodes. Interestingly, p65-Sema3C, but not FR-sema3C, rendered A549 lung cancer cells resistant to serum deprivation, suggesting that previously reported protumorigenic activities of sema3C may be due to p65-Sema3C produced by tumor cells. Our observations suggest that FR-sema3C may be further developed into a novel antitumorigenic drug.
Coeliac disease and schizophrenia
Authors: Eugene B Campbell, Stephen Foley
Journal: BMJ (2004)

Editor—Eaton et al report a strong risk relation between schizophrenia and coeliac disease.1 We do not believe that their data support this hypothesis.

They define their case sample as 7997 patients with schizophrenia, in whom they found four cases of coeliac disease. They then include the data on parents' coeliac status (eight cases) in their analysis, and this is potentially misleading. If the parents' data are excluded from the analysis the prevalence of coeliac disease in people with new onset schizophrenia is only 0.5 per 1000, which is the same as in their control group.

Eaton et al describe coeliac disease as rare in Denmark, which was the traditional view. Their sample population dated from 1981-98, when diagnostic testing for coeliac disease advanced. Recent data using endomysial antibody to screen the Danish population suggests a prevalence of 1 in 400, more akin to neighbouring Scandinavian countries.2 Underascertainment of the true prevalence of coeliac disease is therefore a real possibility and a potential confounding factor.
Differential diagnosis of intestinal Behçet’s disease and Crohn’s disease by colonoscopic findings
Authors: S. Lee, B. Kim, T. Kim, W. Kim
Journal: Endoscopy (2009)

See also: Commentaire de travail de S. K. Lee et al., pp. 9Endoscopy 2009; 41(01): 94-95DOI: 10.1055/s-0032-1306721
Systems biology analysis of immune signaling in peripheral blood mononuclear cells (PBMC) of melanoma patients receiving ipilimumab; basis for clinical response biomarker identification
Authors: Drew Hotson, Ryan Alvarado, Andrew Conroy, Santosh Putta, Ester Simeone, Assunta Esposito, Mariaelena Capone, Gabriele Madonna, Antonio M Grimaldi, David Rosen, Spencer Liang, Alessandra Cesano, Paolo A Ascierto, Rachael Hawtin
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Ipilimumab, an anti-CTLA-4 monoclonal antibody, is approved for treatment of unresectable/metastatic melanoma. Treatment benefits only a subset of patients (pts) and is associated with significant adverse effects. Biomarkers of pt response are needed. Single cell network profiling
Single-Dose Metronidazole for Trichomonal Vaginitis
Authors: Jr . John R. Dykers
Journal: New England Journal of Medicine (1975)

IN the United States, the currently recommended regimen for treating trichomonal vaginitis is metronidazole, 250 mg by mouth three times a day for 10 days.1 Ross, Woodcock, and Csonka report successful therapy of trichomonal vaginitis with a single 2-g dose of metronidazole (Flagyl).2 3 4 Several other short treatment courses have been presented and summarized.5 6 7 8 Reinfection, recurrence because of a relatively alkaline vagina, and persistence of symptoms because of other infections, have been discussed.9 Morton has "concluded that a simple 2 gram treatment schedule with metronidazole is adequate treatment for trichomoniasis in both sexes."10 The rapidly attained high serum level of metronidazole . . .
Effect of the angiotensin II blocker 1-Sar-8-Ala-angiotensin II on renal artery clip hypertension in the rat.
Authors: G J Macdonald, G W Boyd, W S Peart
Journal: Circulation Research (1975)

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.
PMO-095 Laparoscopic vs open pancreaticoduodenectomy: oncological outcomes using leeds pathology protocol (LEEPP)—a matched-pair analysis
Authors: A Hakeem, A Aldouri, A M Smith, K V Menon
Journal: Gut (2012)

<h3>Introduction</h3> Laparoscopic Pancreaticoduodenectomy (LPD) has recently been shown to be a technically safe procedure. Oncological safety of LPD is still a matter for debate. Currently, there is limited evidence for cancer outcomes following LPD, especially in comparison to Open Pancreaticoduodenectomy (OPD). The aim of this study is to compare the adequacy of cancer resection and outcome following LPD and OPD. <h3>Methods</h3> Between November 2005 and April 2009, 12 LPD9s (nine ampullary and three distal Common Bile Duct tumours) were carried out in a tertiary referral centre. A cohort of 12 patients who underwent OPD from November 2003 to February 2007 were matched for age, sex, site of tumour origin and tumour size. Histology was assessed using previously validated Leeds Pathology Protocol (LEEPP) (Ref). The primary aim was to evaluate margin involvement and mean number of lymph nodes excised. The secondary endpoints were complications, high-dependency unit (HDU) stay, length of hospital stay (LOS), recurrence and mortality rate. The median follow-up was 46.8 months for LPD and 56.0 months for OPD. <h3>Results</h3> R0 resection was achieved in 9 LPD vs 8 OPD (p=1.000). The T staging T2, T3, T4 were 6, 4, 2 for LPD vs 6, 5, 1 for OPD respectively (p=1.000). The mean tumour size was 19.8 for LPD Vs 19.2 for OPD (p=0.870). The mean number of lymph node excised for LPD vs OPD (20.7 vs 18.5, p=0.534). Clavien grade I/II complications (5 vs 8), Clavien grade III/IV complications (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean HDU stay was longer in OPD group (3.7 vs 1.4 days, p&lt;0.000), but LOS was no different (14.9 vs 14.9 days, p=1.000). There were two recurrences each in LPD and OPD group (p=1.000). Overall mortality for LPD vs OPD (2 vs 6, p=0.193) and recurrence-related mortality (2 vs 2, p=1.000). <h3>Conclusion</h3> Compared to open procedure, in patients with tumour size &lt;2 cm, laparoscopic pancreaticoduodenectomy achieves similar rate of R0 resection, lymph node harvest and long-term recurrence. LPD patients have significantly shorter high-dependency stay and lesser post-operative complications. Though technically challenging, laparoscopic pancreaticoduodenectomy is safe and does not compromise oncological outcome for tumours &lt;2 cm. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Menon KV</b>, <i>et al.</i> Impact of margin status on survival following pancreaticoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP). HPB (Oxford) 2009;<b>11</b>:18–24.
Natural killer cells involved in lymphomatoid granulomatosis
Authors: J.D. Bos, J.H.Sllevis Smitt, R. Koopmans, P.M. Bakker
Journal: British Journal of Dermatology (1983)

Journal Article Natural killer cells involved in lymphomatoid granulomatosis Get access J.D. Bos, J.D. Bos Departments of Dermatology University of Amsterdam, Academic Medical Center and Wilhelmina Gasthuis, Meibergreef 9, 1195 AZ Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar J.H.Sllevis Smitt, J.H.Sllevis Smitt Departments of Dermatology University of Amsterdam, Academic Medical Center and Wilhelmina Gasthuis, Meibergreef 9, 1195 AZ Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar R. Koopmans, R. Koopmans Departments of Internal Medicine University of Amsterdam, Academic Medical Center and Wilhelmina Gasthuis, Meibergreef 9, 1195 AZ Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.M. Bakker P.M. Bakker Departments of Pathology, University of Amsterdam, Academic Medical Center and Wilhelmina Gasthuis, Meibergreef 9, 1195 AZ Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 4, 1 October 1983, Pages 490–492, https://doi.org/10.1111/j.1365-2133.1983.tb04626.x Published: 01 October 1983
Transient Photopenia of the Femoral Head Following Arthrography
Authors: GERALD A. MANDELL, H THEODORE HARCKE, J RICHARD BOWEN, COLLEEN A. SHARKEY
Journal: Clinical Nuclear Medicine (1989)

In cases of suspected sepsis of the hip, a negative arthrocentesis may precede bone scintigraphy. Routine instillation of contrast material and air for localization and characterization of the hip joint was observed to produce a transient photopenic femoral head on bone scintigraphy. The photopenia, related to venous tamponade created by the temporarily increased intra-articular pressure of the arthrogram, occurs when the isotopic study is performed within a half hour of the arthrocentesis. The cases of four children suspected of having septic arthritis and/or osteomyelitis and ranging in age from 2 to 19 years are presented to illustrate the temporal relationship of reversible femoral head photopenia with sequential arthrocentesis and bone scintigraphy.