tbuckley/cabot-search huggingface dataset:
Gene Expression Profiling for Therapy Prediction in a Breast Cancer Neoadjuvant Therapy Study Applying Docetaxel/Epirubicin/Cyclophosphamide.
Authors: D. Kemming, C. Schlotter, U. Bosse, U. Vogt, H. Muhs, A. von der Assen, B. Brandt
Journal: Cancer Research (2009)

Abstract Background: Gene expression profiling is a powerful tool to identify markers associated with clinical and therapy outcome of cancer patients. Prediction of the response to neoadjuvant regimens remains a persistent challenge. Aim of this ongoing study is the development of a gene set predicting the response of the tumor to a taxane- anthracycline based neoadjuvant chemotherapy.Material and Methods: Microarray expression profiling was performed on biopsy samples from patients before treatment using Human Genome Survey microarrays (HGSM). The protocol for a phase II study was elaborated for the treatment of breast cancer patients suffering from a primary tumor 1.5 cm or inflammatory breast cancer with Docetaxel/Epirubicin/Cyclophosphamide (TEC) prior to surgical treatment. The study was approved by the local ethical committee and all patients signed an informed consent.Results: Overall 80 patients have been enrolled in the presented study. High quality gene expression data were available from 58 patients. Of these patients 21 responded to the TEC regimen (pCR or MIB1 expressing cells in the residual tumor &amp;lt;= 5% and decrease of Mib1-expression &amp;gt;= 20%). Based on the gene-expression profile we were able to identify a preliminary gene set of 150 genes which allows us to separate responding tumors from the non responding ones based on their gene expression profile. A comparable separation of the groups could not achieved by established tumor markers, e.g. ER, PgR, HER2, uPA etc. which are measured simultaneously on the HGSM. Among the genes distinguishing the two groups several genes normally expressed in mononuclear blood cells were identified, pointing to the presence of tumor infiltrating leukocytes, predominantly in the tumors responding the TEC regimen. The presence of these cells has already been verified in a subset of the samples.Conclusion: We identified a gene set which allows to select patients who will benefit from neoadjuvant chemotherapy. Furthermore at least in the so far investigated samples tumor infiltrating leukocytes are significantly more often found in tumors which respond to a taxane- anthracycline based neoadjuvant chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2039.
Return of the "corridors of shame"?
Authors: J. Nicholl, S. Mason
Journal: BMJ (2013)

Emergency department attendances are rising, and a long term solution is needed 

The proportion of patients spending longer than four hours in England’s emergency departments rose steeply in the first quarter of 2013.1 This produced a storm of headlines and commentary and led to the announcement of a major review of urgent and emergency services in England.2 The situation was blamed on an increase in the number of attendances, and this in turn was laid at the door of scapegoats such as general practitioners, out of hours services, NHS 111 services, and even immigrants. 

Several questions arise. Firstly, was the rise in the numbers breaching the four hour target due to rising attendances? Attendances have been rising on average by 1.5-2% a year at least since 1966, when there were less than seven million attendees,3 compared with more than 20 million today. These increases have not occurred equally each year—for example, almost no change was recorded between 1997/8 and 2001/2. So could an unexpectedly large increase in 2012 have caused the disruption? The answer is no—there was actually a small …
Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis
Authors: Toshiaki Kadokami, Kensuke Egashira, Kouichi Kuwata, Yoshihiro Fukumoto, Toshiyuki Kozai, Hiroshi Yasutake, Takeshi Kuga, Hiroaki Shimokawa, Katsuo Sueishi, Akira Takeshita
Journal: Circulation (1996)

Background We previously reported that chronic inhibition of nitric oxide synthesis by administration of N ω -nitro- l -arginine methyl ester (L-NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model. Methods and Results Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 μg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater ( P &lt;.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT 2 antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT 1 /5-HT 2 antagonist. The decrease in CBF caused by prostaglandin F 2α and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists. Conclusions These results suggest that the 5-HT–induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT 1 receptors in microvascular smooth muscle cells in our animal model.
Cockatiel-induced hypersensitivity pneumonitis.
Authors: James D McCluskey, Robert R Haight, Stuart M Brooks
Journal: Environmental Health Perspectives (2002)

Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.
The homeobox transcription factor VentX controls human macrophage terminal differentiation and proinflammatory activation
Authors: Xiaoming Wu, Hong Gao, Weixiong Ke, Roger W. Giese, Zhenglun Zhu
Journal: Journal of Clinical Investigation (2011)

Macrophages are critical players in both innate and adaptive immunity. While the exogenous signaling events leading to the terminal differentiation of macrophages from monocytes have been studied extensively, the underlying intracellular transcriptional mechanisms remain poorly understood. Here we report that the homeobox transcription factor VentX plays a pivotal role in human macrophage terminal differentiation and proinflammatory function. Our study showed that VentX expression was upregulated upon human primary monocyte-to-macrophage differentiation induced by cytokines such as M-CSF, GM-CSF, and IL-3. Moreover, ablation of VentX expression in primary monocytes profoundly impaired their differentiation to macrophages, and ectopic expression of VentX in a myeloid progenitor cell line triggered its differentiation with prominent macrophage features. Further analysis revealed that VentX was pivotal for the proinflammatory response of terminally differentiated macrophages. Mechanistically, VentX was found to control expression of proteins key to macrophage differentiation and activation, including M-CSF receptor. Importantly, preliminary analysis of gene expression in leukocytes from patients with autoimmune diseases revealed a strong correlation between levels of VentX and those of proinflammatory cytokines. Our results provide mechanistic insight into the crucial roles of VentX in macrophage differentiation and proinflammatory activation and suggest that dysregulation of VentX may play a role in the pathogenesis of autoimmune diseases.
DO VIVISECTORS INFLICT UNNECESSARY SUFFERING IN THEIR INVESTIGATIONS?
Authors: E. STUVER
Journal: JAMA (1898)

About July 18, 1897, there was published in the<i>Rocky Mountain News</i>, an article by E. K. Whitehead, secretary of the Colorado Humane Society, followed on August 30 by another. In these articles the scientific experimenters of the world are directly charged with brutal, inhuman, wanton and cruel conduct toward animals, in carring out their experiments and investigations. Physicians are charged with being participators or accomplices in these so-called atrocities, and it is claimed that no real advance in medical knowledge, which could not have been made without it, has followed as a result of vivisection. The charge that physicians, without sufficient cause, sanction wanton or cruel treatment, or animal mutilations and sufferings which are unnecessary, is a gratuitous insult to a profession animated by the most self-sacrificing and humane instincts of any class of people in the world, a profession which has done more to alleviate human suffering, stay
Management for Doctors: Getting the best from people
Authors: A. V. Owen
Journal: BMJ (1995)

Aside from the many personal tragedies which they cause, premature deaths among able bodied people also have economic consequences.Taking account of that fact, official demographers have calculated data which underline the vast annual loss oflabour potential.According to a press report, in 1991 premature deaths accounted for a loss of 2-23 million man years of working life.4That figure included 102 million man years lost which were ascribable to deaths from accidents, poisoning, and trauma.Of those deaths, as many as 52-4% occurred in people who were drunk.Broadening the focus, that report also implicated alcohol in violent deaths and referred to the role of alcohol in aggravating deaths from cardiovascular, gastrointestinal, and other diseases.Furthermore, it drew attention to the deaths of sober people caused by people who are drunk.Overall the destruction of life was such that in 1991 "more than a quarter of the labour potential in Russia was lost in connection with deaths which were caused predominantly by alcohol."
Hepatoprotection with tauroursodeoxycholate and muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways
Authors: P Milkiewicz, M G Roma, E Elias, R Coleman
Journal: Gut (2002)

Tauroursodeoxycholate (TUDC) provides partial protection against taurolithocholate (TLC) induced cholestasis, possibly by inducing a signalling cascade activating protein kinase C (PKC). The potential protective effects of beta muricholic acid (beta-MC), another 7-beta-hydroxylated bile salt, have not previously been studied in TLC cholestasis.To study the effect of beta-MC on TLC induced cholestasis and also to investigate further the effects of agents affecting intracellular signalling, notably DBcAMP (a cell permeable cAMP analogue) and several protein kinase inhibitors.Functional studies were carried out analysing the proportion of hepatocyte couplets able to accumulate the fluorescent bile acid analogue cholyl-lysyl-fluorescein (CLF) into their sealed canalicular vacuole (cVA of CLF assay).It was found that both beta-MC and DBcAMP were as effective as TUDC in protecting against TLC induced cholestasis. The PKC inhibitors staurosporin and H7 but not the specific protein kinase A (PKA) inhibitor KT5720 abolished the protective effects of TUDC and beta-MC. BAPTA/AM, a chelator of intracellular Ca(2+), significantly decreased the protective effect of both bile salts, and that of DBcAMP. PKC and PKA inhibitors had no effect on protection with DBcAMP.Beta-MC was as effective as TUDC in protecting against TLC cholestasis. Mobilisation of Ca(2+) and activation of PKC, but not of PKA, are involved in the anticholestatic effect of the two 7-beta-hydroxylated bile salts. The hepatoprotective effects of DBcAMP involved Ca(2+) mobilisation, but not PKC or PKA activation.
Exercise before or after refeeding prevents refeeding-induced recovery of cell size after fasting with a different pattern of metabolic gene expressions in rat epididymal adipocytes
Authors: Takuya Sakurai, Megumi Takei, Junetsu Ogasawara, Hiroshi Ueda, Takako Kizaki, Hideki Ohno, Tetsuya Izawa
Journal: Metabolism (2007)
Urinary <i>chiro</i>-Inositol Excretion is an Index Marker of Insulin Sensitivity in Japanese Type II Diabetes
Authors: Susumu Suzuki, Hiromasa Kawasaki, Yoshinori Satoh, Masataka Ohtomo, Masashi Hirai, Aki Hirai, Satoshi Hirai, Masatoshi Onoda, Masahiro Matsumoto, Yoshinori Hinokio, Hiroaki Akai, James Craig, Joseph Larner, Takayoshi Toyota
Journal: Diabetes Care (1994)

To determine the relationship between urinary chiro-inositol excretion and insulin sensitivity in Japanese type II diabetic patients.Eighteen subjects were age-matched, nonobese, type II diabetic patients. Eight subjects had impaired glucose tolerance (IGT), and 10 had normal glucose tolerance (NGT). We quantified urinary chiro-inositol excretion using gas chromatography-mass spectrometry and the insulin sensitivity index (SI), and glucose effectiveness (SG) using Bergman's modified minimal model method.The urinary excretion of chiro-inositol was much lower in the diabetic patients (32.3 +/- 16.0 mumol/day, means +/- SD) than in the NGT subjects (96.0 +/- 17.6; P < 0.0001) and IGT subjects (58.9 +/- 11.6; P < 0.0001). SI was much lower in the diabetic patients (3.81 +/- 1.49) than in the NGT subjects 6.30 +/- 1.59, P < 0.0005). SG was much lower in the diabetic patients (2.14 +/- 0.56) than in the NGT subjects (3.07 +/- 0.38, P < 0.0001). There was a significant correlation between urinary chiro-inositol excretion and SI (r = 0.766), as well as a significant correlation between urinary chiro-inositol excretion and SG (r = 0.747).
Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia
Authors: Soheil Meshinchi, Derek L. Stirewalt, Todd A. Alonzo, Quangeng Zhang, David A. Sweetser, William G. Woods, Irwin D. Bernstein, Robert J. Arceci, Jerald P. Radich
Journal: Blood (2003)
Diabetes after infectious hepatitis: a follow-up study.
Authors: J M Oli, C Nwokolo
Journal: BMJ (1979)

Eleven patients (nine men, one woman, and one girl) aged 11-62 years who developed diabetes mellitus after an attack of infectious hepatitis during the Eastern Nigerian epidemic of 1970-2 were followed up for two to nine years. One patient aged 60 years remained diabetic after the original illness. In the remaining 10 patients the diabetes remitted after three to nine months (mean 6.7 months) but in four it recurred after a remission lasting one and a half to four years (mean 2.6 years). Results of this follow-up study seem to confirm that the pancreas is sometimes permanently damaged during infectious hepatitis.
Perceived Parental Attitude, Alexithymia and Defense Style in Psychiatric Outpatients
Authors: C.G. Kooiman, Ph. Spinhoven, R.W. Trijsburg, H.G.M. Rooijmans
Journal: Psychotherapy and Psychosomatics (1998)

Although it is the clinical impression that alexithymia may be due to disturbances in the early parent-child relationship and that it is associated with primitive defense mechanisms, a possible association with neurotic defense mechanisms, such as repression and reaction formation, has also been mentioned. However, empirical studies on these and related issues are scarce. The aim of this study was to determine the association between perceived parental attitude, defense mechanisms and alexithymia.In a cross-sectional study we obtained data from 78 psychiatric outpatients. Alexithymia, defense mechanisms and perceived parental attitude were measured with the Toronto Alexithymia Scale, the Defense Style Questionnaire and the Parental Bonding Instrument.We found only weak associations between perceived parental attitude and alexithymic features. Primitive and adaptive defenses were associated with alexithymic features in a clinically sensible way. The strongest association was found between primitive defense mechanisms and alexithymic features. There was hardly any association between neurotic defense mechanisms and alexithymic features.The results of our study support the hypothesis that alexithymia is associated with a primitive defense style, whereas a relation to disturbances in early parent-child relationship could not be confirmed. It is argued that possibly more severe traumatic experiences, such as physical and sexual abuse, than merely a negatively perceived parental attitude, are necessary to develop alexithymic features.
Landmark perspective. Sickle cell anemia
Authors: C. S. Johnson
Journal: JAMA (1985)

IN THIS issue, the editors of JAMA have reprinted an article that stands as a landmark in medical history. This article, which first appeared in The Journal 63 years ago, is a detailed account of the clinical course of the first patient recognized with sickle cell anemia at The Johns Hopkins Hospital. <h3>History</h3> Verne R. Mason was in residency training at the time and reported this case in detail because of its supposed rarity and to draw attention to the disease as a clinical entity. In addition, he was the first to use the term<i>sickle cell anemia</i>, deriving it from the description of the cells in Herrick's1 original report. In his report, Mason recognized that the disease was a lifelong condition and probably inherited and that the reticulocyte count was elevated, although he did not conclude that the anemia was hemolytic (leaving that to his classmate, Sydenstricker). Furthermore, he
Airway Complications Following Pediatric Lung and Heart–Lung Transplantation
Authors: ATHANASIOS G. KADITIS, MAGDALEN GONDOR, PATRICIA A. NIXON, STEVEN WEBBER, ROBERT J. KEENAN, ROBIN KAYE, GEOFFREY KURLAND
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Obstruction at the airway anastomosis is a recognized complication of adult heart-lung transplantation (HLT) and lung transplantation (LT). Data for pediatric transplantation have been scarce. We reviewed our experience in pediatric HLT and LT to determine the frequency of airway complications and to document the therapeutic modalities used for their treatment. Fifty-three patients (median age: 13.8 yr; range: 1.3 to 28.2 yr) underwent HLT (n = 25), SLT (n = 3), DLT (n = 25), or repeat DLT (n = 3) and survived for more than 72 h. Major anastomotic airway complications requiring intervention affected one of the 25 HLT (4%) and seven of the 28 LT (SLT + DLT) patients (25%) (p = 0.05). Four patients with granulation tissue occluding the airway were treated with forceps resection, laser ablation, or balloon dilatation. Three patients with fibrotic strictures received silicone stents, laser ablation, or balloon dilatation. Two patients with bronchomalacia or diffuse stricture below the anastomosis underwent metal stent placement. Five of seven patients who were treated for anastomotic complications had satisfactory relief of airway obstruction. As compared with previously studied adults, pediatric heart-lung transplant recipients had the same or a lower frequency, and pediatric lung transplant recipients had a higher frequency of major anastomotic airway complications. A variety of treatment modalities were necessary to achieve adequate relief of airway obstruction.
The Myth of Red Urine due to Phenytoin
Authors: Bennett M. Derby
Journal: JAMA (1983)

WE WERE recently struck agog to find recorded in a current text of urology that, in the presence of an acid urinary pH, phenytoin (Dilantin, Parke-Davis) will result in a red urine.<sup>1</sup>This potentially electrifying information is applicable to thousands of patients in whom the differential diagnosis of hematuria or hemoglobinuria might arise and for whom medical investigation and reassurance might be necessary on a large scale. The phenomenon, however, is not mentioned in many other sources on discoloration of urine and on phenytoin and is unmentioned in Parke-Davis product information. It is unheard of in the practice of neurologists queried, covering a period of practice of many years that encompassed a vast number of individuals with seizure disorder. The author of the cited urology chapter has himself never seen a patient receiving phenytoin who has red urine and was unable to recall the reference from which his information
Hybrid natural orifice transluminal endoscopic surgery (NOTES) for Roux-en-Y gastric bypass: an experimental surgical study in human cadavers
Authors: M. Hagen, O. Wagner, P. Swain, F. Pugin, N. Buchs, M. Caddedu, P. Jamidar, J. Fasel, P. Morel
Journal: Endoscopy (2008)

See also: Commentaire de travail de M. E. Hagen et al., pp. 918Endoscopy 2008; 40(11): 1058-1059DOI: 10.1055/s-0032-1306888
Percutaneous transluminal angioplasty of the arteries of the lower limbs: a 5 year follow-up.
Authors: A Gallino, F Mahler, P Probst, B Nachbur
Journal: Circulation (1984)

A total of 482 percutaneous transluminal angioplasties (PTAs) of the arteries of the lower limbs were performed in 411 patients between 1977 and 1983. The 5 year patency rate, calculated by the life table method, was 83% for iliac and 58% for femoropopliteal PTA. Clinical improvement after the procedure was confirmed by a significant drop of the arm-ankle pressure difference: 48 +/- 5 mm Hg before vs 17 +/- 5 mm Hg 2 years after iliac PTA (p less than .01) and 73 +/- 5 mm Hg before vs 28 +/- 6 mm Hg after femoropopliteal PTA (p less than .01). The majority of reocclusions occurred within the first year after angioplasty. Patients with stenoses or occlusions of less than 3 cm had a favorable long-term patency rate of 74%. Conversely, patients with femoropopliteal occlusions presenting with pain at rest, diabetes, occlusions of greater than 3 cm, or poor distal runoff had an elevated rate of reocclusion. Complications, which occurred in 8% of the patients in whom PTA was attempted, included local hemorrhage, dissection, embolism, and spasm necessitating surgical intervention in 2%. No deaths or amputations were a direct consequence of PTA. PTA of arteries of the lower limbs may thus be regarded as a valid complementary treatment to vascular surgery in patients with occlusive disease of the peripheral arteries.
INFECTIOUS MYXOMATOSIS OF RABBITS
Authors: Thomas M. Rivers, S. M. Ward, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1939)

The soluble antigen of myxoma is a heat-labile protein which has an isoelectric point near pH 4.5 and is precipitated from half saturated solutions of ammonium sulfate. It can be partially purified by methods of differential precipitation based on variations in the pH and electrolyte concentration. Rabbits receiving the labile, soluble substance of myxoma develop homologous precipitins and their serum agglutinates elementary bodies of myxoma, provided the dermal pulp from which the bodies are obtained contains the soluble substance; neutralizing antibodies do not appear, however, and the animals are not resistant to infection with the virus of myxoma. Elementary bodies of myxoma appear to have a heat-stable agglutinogen that operates when brought in contact with serum from animals recovered from myxoma, but little, if at all, when in contact with anti-soluble substance serum.