tbuckley/cabot-search huggingface dataset:
Preoperative Distress Predicts Persistent Pain After Breast Cancer Treatment: A Prospective Cohort Study
Authors: Mathias Kvist Mejdahl, Birgitte Goldschmidt Mertz, Pernille Envold Bidstrup, Kenneth Geving Andersen
Journal: Journal of the National Comprehensive Cancer Network (2015)

Purpose: Persistent pain after breast cancer treatment (PPBCT) affects 25% to 60% of breast cancer survivors and is recognized as a clinical problem, with 10% to 15% reporting moderate to severe pain several years after treatment. Psychological comorbidity is known to influence pain perception, and evidence links signs of depression and anxiety with development of PPBCT. The purpose of this study was to assess preoperative distress as a predictive factor for development of PPBCT. Methods: Between October 2008 and October 2009, 426 women diagnosed with primary breast cancer, undergoing surgery at the Department of Breast Surgery, Rigshospitalet, Denmark, were invited to participate in the study. Patients filled out a questionnaire preoperatively, and 4 and 8 months after surgery. Preoperative distress was measured with the Distress Thermometer (DT; 11-point scale, 0–10). We examined the association between severe preoperative distress (using DT ≥7) and moderate to severe PPBCT 8 months after diagnosis using a logistic regression model. Results: A total of 357 patients participated in this study and 291 (82%) returned all follow-up questionnaires. Preoperative distress was significantly associated with moderate to severe PPBCT at 8 months, with an adjusted odds ratio (OR) of 2.05 (95% CI, 1.18–3.59; P=.01), and at 4 months, with an OR of 2.23 (95% CI, 1.23–4.05; P=.01). Conclusions: Preoperative distress was associated with PPCBT, suggesting distress as an independent risk factor for PPBCT. Preoperative identification of patients at risk for PPBCT allows for further research in psychological and pharmacological treatment of this condition.
Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage
Authors: Elise S Demitrack, Eitaro Aihara, Susan Kenny, Andrea Varro, Marshall H Montrose
Journal: Gut (2011)

<h3>Background and aims</h3> The authors9 goal was to measure pH at the gastric surface (pH<sub>o</sub>) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. <h3>Methods</h3> Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pH<sub>o</sub>. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. <h3>Results</h3> Similar rates of epithelial repair and resting pH<sub>o</sub> values (∼pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pH<sub>o</sub> was lower (2.5±0.2, <i>P</i> &lt;0.05 vs pH 3). Epithelial repair was slower at luminal pH 7 and pH<sub>o</sub> was higher (6.4±0.1, <i>P</i>&lt;0.001). In all conditions, pH<sub>o</sub> increased adjacent to damage. At luminal pH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. <h3>Conclusions</h3> Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH.
Malarial Acute Renal Failure
Authors: RASHAD S. BARSOUM
Journal: Journal of the American Society of Nephrology (2000)

Malaria is an Italian word composed of “ mala ” and “ aria,” derived from malus (bad), and aeris (air). It was first used to describe a fever (miasma), which was wrongly attributed to exposure to poisonous air rising from marshes. Although the disease had been described in the Hippocratic Collection (460 to 377 BC) and its relation to mosquitoes suggested in the 5th century AD, by the Indian physician Susruta, it was only in 1880 that Charles Laveran, a French physician working in Algeria, discovered the true causative agent as being a sporozoan of the genus Plasmodium. More than a century later, we got to map the malaria genome, identifying a huge number of genes located on 14 chromosomes. Malaria is acquired through the sting of an infected Anopheles mosquito, which injects the sporozoites into the host’s dermis. These are carried with the blood stream to the liver, where they mature in the hepatocytes (extra-erythrocytic cycle) to tissue schizonts that release their merozoites into the hepatic sinusoids. The latter invade the red cells, starting the erythrocytic cycle, which comprises ring forms, trophozoites, and, subsequently, schizonts that contain a new generation of merozoites. The parasitized cells are induced by plasmodial DNA to develop a microtubular system that conveys nutrients to the parasite. They eventually rupture and release the merozoites, which repeat the same cycle. A few merozoites are sexually differentiated into male and female gametocytes, which are essential for the completion of the sexual cycle in the vector.
George R Tiller
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

US doctor who provided late abortions and was murdered 

Dr George Tiller, one of only three US doctors who provided abortions late in pregnancy, was shot dead as he served as an usher in his church in Wichita, Kansas, on 31 May ( BMJ 2009;338:b2237, doi:10.1136/bmj.b2237). At his funeral on 7 June, more than 800 people filled the sanctuary at the College Hill United Methodist Church while hundreds of others crowded into an overflow room or church hallways, including women whom he had treated. Police kept a few antiabortion demonstrators blocked away. His wife, Jeanne, sang the Lord’s Prayer and dedicated it to “my best buddy and the love of my life,” according to the New York Times (www.nytimes.com, 7 June 2009, “Kansas doctor remembered as devoted to family and women”).

Tiller was no stranger to violence. In 1993 he was shot in both arms; his assailant was convicted and imprisoned. The clinic was vandalised last month. In 1986 it was bombed. Dr Tiller usually wore a flak jacket and drove an armour plated Jeep.

President Barack Obama said that he was “shocked and outraged” by the killing. The Planned Parenthood Federation, the National Partnership for Women and Families, the Guttmacher Institute, the Center for Reproductive Rights, the National Abortion Federation, Physicians for Reproductive Choice and Health, NARAL Pro-Choice America, and other reproductive health groups expressed their sorrow at the killing.

Many …
Modification of the Antidiuretic Effect of Vasopressin by Acid and Alkaline Loads*
Authors: T. D. Ullmann, W. J. Czaczkes, J. Menczel
Journal: Journal of Clinical Investigation (1965)

Hypotonic solutions of sodium chloride, ammonium chloride, and sodium bicarbonate were infused at a rate of 7.4 ml per minute, with a Bowman constant infusing pump.The solutions were made up to contain 100 mOsm per L of the electrolyte solution and 100 mOsm per L of glucose.Thus, the amount of electrolytes infused was 740 AOsm per minute.Inulin was added to the infusion
Death to some cliches
Authors: J. Verbov
Journal: Journal of the Royal Society of Medicine (2006)

I agree with Dr Forgacs (December 2005 JRSM1) that referring to a patient as being `haemodynamically stable' is unacceptable and the offending practitioner should be requested to return to basics and provide actual values.

However, I admit to being fond of `common things occur commonly' and the similar `when you hear the sound of hooves, don't look for zebras', both of which, in the thinking individual, do not exclude the uncommon diagnosis. I also believe that `irregular irregularity' is perfectly acceptable when describing a pulse or a magnified abnormal volar skin appearance.

What about cliches in general? `See you later' annoys when, as is often the case, the speaker is unlikely to see you again. The simile cliche `bald as a coot' may sometimes be accurate but it is a rude expression ready for burial. `Quality of life' is expanding its meaning as it becomes overused, and its use should be restricted.

Other cliches are no doubt `in the pipeline'. Unoriginal and trite they may be, but many still deserve `tender loving care' (Henry VI Part ii Act 3 Sc.2).
Temporal Lobe Abnormalities in First-Episode Psychosis
Authors: Alex Sumich, Xavier A Chitnis, Dominic G Fannon, Séamus O'Ceallaigh, Victor C Doku, Abi Falrowicz, Nicolette Marshall, Vallakalil M Matthew, Mark Potter, Tonmoy Sharma
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The nature and time course of temporal lobe abnormalities in psychotic illness remain controversial. Confounds include disease chronicity, gender, and handedness. The present study investigated temporal substructures in right-handed male patients experiencing their first episode of psychotic illness. METHOD: Magnetic resonance imaging scans were obtained for 25 minimally treated patients experiencing their first psychotic episode and 16 healthy comparison subjects. Group differences in volumes of the hippocampus, amygdala, planum temporale, and Heschl's gyrus were tested. RESULTS: The patients had smaller bilateral hippocampal and left planum temporale volumes than the comparison subjects. Paranoid and nonparanoid patients differed in left amygdala volume. CONCLUSIONS: The authors conclude that bilateral hippocampal and left planum temporale abnormalities are present near the onset of psychosis.
Effects of quinidine on atrioventricular nodal reentrant paroxysmal tachycardia.
Authors: D Wu, J S Hung, C T Kuo, K S Hsu, W B Shieh
Journal: Circulation (1981)

Electrophysiologic studies were performed in 14 patients with atrioventricular nodal reentrant paroxysmal tachycardia (PSVT) before and after oral administration of 1.2-1.6 g quinidine sulfate over a 24-hour period (0.3-0.4 g every 6 hours). Studies were performed after 0.5-1 mg i.v. atropine before and after quinidine. All 14 patients had induction of sustained PSVT before quinidine, with or without atropine. After quinidine, 11 patients lost the ability to induce echoes or sustain PSVT, reflecting depression of the retrograde pathway with either absence of atrial echoes (six patients) or induction of nonsustained PSVT, with termination of echoes or PSVT occurring after QRS (block in retrograde pathway) (five patients). In only one of these 11 patients was sustained PSVT inducible after addition of atropine. All 11 were discharged on the same dose of quinidine. In three patients, quinidine was discontinued because of side effects. Follow-up in the remaining eight patients for 8 +/- 2 months showed no recurrence of sustained PSVT. Three of the 14 patients had induction of sustained PSVT after quinidine. Ventricular paced cycle length producing ventriculoatrial block was 314 +/- 7 msec (mean +/- SEM) before and 392 +/- 13 msec after quinidine (p less than 0.01) in the 14 patients, suggesting depression of the retrograde pathway with quinidine. In summary, quinidine inhibited induction of sustained atrioventricular nodal reentrant tachycardia with depression of the retrograde pathway. It is very effective in preventing recurrence of PSVT in most patients.
Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy
Authors: A.D. Vidal, G.N. Thalmann, E. Karamitopoulou-Diamantis, M.F. Fey, U.E. Studer
Journal: Annals of Oncology (2014)
Lack of Association of Single-Nucleotide Polymorphisms in <i>Pregnane X Receptor, Hepatic Nuclear Factor 4α</i>, and <i>Constitutive Androstane Receptor</i> with Docetaxel Pharmacokinetics
Authors: Lai-San Tham, Nicholas H.G. Holford, Sok-Ying Hor, Theresa Tan, Lingzhi Wang, Rui-Chen Lim, How-Sung Lee, Soo-Chin Lee, Boon-Cher Goh
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study aims to describe a population pharmacokinetic model for docetaxel in Asian breast cancer patients and to evaluate the effects of single-nucleotide polymorphisms (SNP) in the cytochrome P450 3A (CYP3A) gene expression regulators, constitutive androstane receptor (CAR), pregnane X receptor (PXR), and hepatic nuclear factor 4α (HNF4α), on the pharmacokinetics of docetaxel. Experimental Design: Docetaxel was given as an i.v. infusion of 75 mg/m2 over 1 h to 101 female breast cancer patients. CAR, PXR, and HNF4α were comprehensively sequenced. Docetaxel concentrations were measured using a liquid chromatography/tandem mass spectrometry method and its population pharmacokinetic variables, and the covariate effects of clearance predictors were estimated using a nonlinear mixed effects model. Results: Final estimates for docetaxel clearance was 47.1 L/h/70 kg/1.75 m. Between subject variability in docetaxel clearance was 22.5%. Covariates that showed significant association with docetaxel clearance included body size, α1 acid glycoprotein and liver function. SNPs identified in the coding regions of CAR and HNF4α and 5′ untranslated region of PXR in this Asian breast cancer cohort did not seem to improve predictability of docetaxel clearance. Conclusions: SNPs identified in CYP3A gene expression regulators CAR, HNF4α, and PXR in the Asian female breast cancer population do not seem to have any significant effect on the clearance of docetaxel, a CYP3A substrate.
Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease
Authors: E Savarino, D Pohl, P Zentilin, P Dulbecco, G Sammito, L Sconfienza, S Vigneri, G Camerini, R Tutuian, V Savarino
Journal: Gut (2009)

<h3>Introduction:</h3> Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. <h3>Aim:</h3> To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). <h3>Methods:</h3> Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. <h3>Results:</h3> Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p&lt;0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. <h3>Conclusion:</h3> The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux.
Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice
Authors: Kai Zhang, Susan L.E. Loong, Steve Connor, Sidney W.K. Yu, Soo-Yong Tan, Robert T.H. Ng, Khai Mun Lee, Leigh Canham, Pierce K.H. Chow
Journal: Clinical Cancer Research (2005)

Abstract Purpose: 32P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32phosphorus (32P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study. Methods: Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice. When the implanted tumors were ∼1 cm in diameter, 32P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis. Results: 32P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group. Conclusion: 32P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.
Biosynthesis of cytidine diphosphate diglyceride by human platelets
Authors: Frank L. Call, William J. Williams
Journal: Journal of Clinical Investigation (1970)

Homogenates of human platelets contain an enzyme which catalyzes the formation of cytidine diphosphate diglyceride from cytidine triphosphate and phosphatidic acid. The enzymatic activity could not be dissociated from platelet particles and the greatest specific activity was found in the membrane fraction. The K(m) for cytidine triphosphate was 0.16 mmole/liter and the apparent K(m) for phosphatidic acid was 6.2 mmoles/liter. The pH optimum was 7.0 and the most effective buffers were triethanolamine-HCl and Tris-HCl. The reaction was dependent on the presence of divalent cations, magnesium being the most effective of those investigated. Monovalent cations did not alter the reaction rate. Evidence is presented that the cytidine diphosphate diglyceride produced can serve as a precursor for the synthesis of phosphatidylinositol. No difference was found in the enzymatic activity in platelets from normal subjects and from patients with diseases known to interfere with platelet thromboplastic function.
IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Courtney Smith, Mee Young Chang, Katherine H. Parker, Daniel W. Beury, James B. DuHadaway, Hollie E. Flick, Janette Boulden, Erika Sutanto-Ward, Alejandro Peralta Soler, Lisa D. Laury-Kleintop, Laura Mandik-Nayak, Richard Metz, Suzanne Ostrand-Rosenberg, George C. Prendergast, Alexander J. Muller
Journal: Cancer Discovery (2012)

Abstract Indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have entered clinical trials for cancer treatment based on preclinical studies, indicating that they can defeat immune escape and broadly enhance other therapeutic modalities. However, clear genetic evidence of the impact of IDO on tumorigenesis in physiologic models of primary or metastatic disease is lacking. Investigating the impact of Ido1 gene disruption in mouse models of oncogenic KRAS-induced lung carcinoma and breast carcinoma–derived pulmonary metastasis, we have found that IDO deficiency resulted in reduced lung tumor burden and improved survival in both models. Micro-computed tomographic (CT) imaging further revealed that the density of the underlying pulmonary blood vessels was significantly reduced in Ido1-nullizygous mice. During lung tumor and metastasis outgrowth, interleukin (IL)-6 induction was greatly attenuated in conjunction with the loss of IDO. Biologically, this resulted in a consequential impairment of protumorigenic myeloid-derived suppressor cells (MDSC), as restoration of IL-6 recovered both MDSC suppressor function and metastasis susceptibility in Ido1-nullizygous mice. Together, our findings define IDO as a prototypical integrative modifier that bridges inflammation, vascularization, and immune escape to license primary and metastatic tumor outgrowth. Significance: This study provides preclinical, genetic proof-of-concept that the immunoregulatory enzyme IDO contributes to autochthonous carcinoma progression and to the creation of a metastatic niche. IDO deficiency in vivo negatively impacted both vascularization and IL-6–dependent, MDSC-driven immune escape, establishing IDO as an overarching factor directing the establishment of a protumorigenic environment. Cancer Discov; 2(8); 722–35. ©2012 AACR. Read the Commentary on this article by Novitskiy et al., p. 673. This article is highlighted in the In This Issue feature, p. 653.
Cytomegalovirus as an Etiologic Factor in Corneal Endotheliitis
Authors: Noriko Koizumi, Takashi Suzuki, Toshihiko Uno, Hidemi Chihara, Atsushi Shiraishi, Yuko Hara, Tsutomu Inatomi, Chie Sotozono, Satoshi Kawasaki, Kenta Yamasaki, Chikako Mochida, Yuichi Ohashi, Shigeru Kinoshita
Journal: Ophthalmology (2007)
Interleukin-8 Mediates Resistance to Antiangiogenic Agent Sunitinib in Renal Cell Carcinoma
Authors: Dan Huang, Yan Ding, Ming Zhou, Brian I. Rini, David Petillo, Chao-Nan Qian, Richard Kahnoski, P. Andrew Futreal, Kyle A. Furge, Bin Tean Teh
Journal: Cancer Research (2010)

The broad spectrum kinase inhibitor sunitinib is a first-line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients develop sunitinib resistance and progressive disease after about 1 year of treatment. In this study, we evaluated the mechanisms of resistance to sunitinib to identify the potential tactics to overcome it. Xenograft models were generated that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, indicating that an escape from antiangiogenesis occurred. Notably, escape coincided with increased secretion of interleukin-8 (IL-8) from tumors into the plasma, and coadministration of an IL-8 neutralizing antibody resensitized tumors to sunitinib treatment. In patients who were refractory to sunitinib treatment, IL-8 expression was elevated in ccRCC tumors, supporting the concept that IL-8 levels might predict clinical response to sunitinib. Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy.