tbuckley/cabot-search huggingface dataset:
Increased Matrix Metalloproteinase Activity and Selective Upregulation in LV Myocardium From Patients With End-Stage Dilated Cardiomyopathy
Authors: Chadwick V. Thomas, Mytsi L. Coker, James L. Zellner, John R. Handy, A. Jackson Crumbley, Francis G. Spinale
Journal: Circulation (1998)

Background —One of the hallmarks of dilated cardiomyopathy (DCM) is left ventricular (LV) remodeling. The matrix metalloproteinases (MMPs) are a family of enzymes that contribute to extracellular remodeling in several disease states. Additionally, a family of inhibitors called tissue inhibitors of MMPs (TIMPs) has been shown to exist and to tightly regulate MMP activity. However, the types of MMPs and TIMPs expressed within the normal and DCM LV myocardium and the relation to MMP activity remain unexplored. Methods and Results —Relative LV myocardial MMP activity was determined in the normal (n=8) and idiopathic DCM (n=7) human LV myocardium by substrate zymography. Relative LV myocardial abundance of interstitial collagenase (MMP-1), stromelysin (MMP-3), 72 kD gelatinase (MMP-2), 92 kD gelatinase (MMP-9), TIMP-1, and TIMP-2 were measured with quantitative immunoblotting. LV myocardial MMP zymographic activity increased with DCM compared with normal (984±149 versus 413±64 pixels, P &lt;.05). With DCM, LV myocardial abundance of MMP-1 decreased to 16±6% ( P &lt;.05), MMP-3 increased to 563±212% ( P &lt;.05), MMP-9 increased to 422±64% ( P &lt;.05), and MMP-2 was unchanged when compared with normal. LV myocardial abundance of TIMP-1 and TIMP-2 increased by &gt;500% with DCM. A high-molecular-weight immunoreactive band for both TIMP-1 and TIMP-2, suggesting a TIMP/MMP complex, was increased &gt;600% with DCM. Conclusions —This study demonstrated increased LV myocardial MMP activity and evidence for independent regulatory mechanisms of MMP and TIMP expression with DCM. These findings suggest that selective inhibition of MMP species within the LV myocardium may provide a novel therapeutic target in patients with DCM.
Needs of Junior Hospital Doctors
Authors: D. E. F. Newton
Journal: BMJ (1974)

SIR,-In your leading article (26 October, p. 177) it is stated that "tricyclic compounds are ineffective, though no controlled trial has yet been reported."Tricyclic drugs have been widely used in phobic states and there is in fact growing and extensive evidence of the value of clomipramine in the treatment of such disorders.The value of this drug was first reported in 19711 and subsequent work2-4 has substantiated these findings.In an interim report on the use of clomipramine in phobic and obsessional disorders5 I stated that in the 15 cases reviewed phobic anxiety showed an improvement of 60%/.after six weeks.A further report is awaiting publication on 32 patients suffering from phobic anxiety who were admitted to an open multicentre trial.There was an improvement in all phobias, in situational anxiety, in interference, and in autonomic side effects in all the 27 patients who completed the six-week period of the -trial.-Iam, etc.,
Size of moles linked to melanoma risk
Authors: N. Macready
Journal: BMJ (1997)

The size, type, and number of moles on a person's skin may reflect his or her risk of melanoma, according to researchers. They say that this relation could help doctors to identify high risk individuals and design better programmes for detecting melanoma, which is highly curable in its early stages.

The investigators interviewed 738 consecutive patients with newly diagnosed melanoma identified at two melanoma centres in the United States between 1 January 1991 and 31 December 1992, …
Information for managers in hospitals: representing maternity unit statistics graphically.
Authors: A Szczepura, M Mugford, J A Stilwell
Journal: BMJ (1987)

Staff who organise and run maternity units contribute many statistics to their health authority but do not find it easy to obtain information about their unit from these statistics. Data that are collected routinely, however, can be used to provide each unit with a graphical profile of its activity and resources. The method described here was derived from the personality profiles used by psychologists and allows staff in one unit to assess the outcome, activity, and use of resources in their unit in relation to similar units, to explain some of the differences when these occur, or to highlight potential problems. Examples are taken from a study of maternity units in the West Midlands. It is concluded that the technique can indicate potential problems and usefully be adopted by those who monitor maternity care in districts or hospitals.
Trypanosomiasis and Morbus Dormitiva
Authors: Alex. Maxwell
Journal: BMJ (1904)

Here we have a young man apparently in good health without any preliminary signs or symptoms of lead poisoning, suddenly struck down by the most severe of convulsions, which terminate in his death.Has lead a special predilec- tion for the nervous system in certain individuals?If so, are we to regard the convulsions as due to the direct irrita- tion of the lead upon the nervous system, or may we look upon the convulsions, as in the case of uraemia, due to auto- intoxication from the retention of harmful substances due to defective renal metabolism?REFERENCES.
High-Dose Epinephrine in Cardiopulmonary Resuscitation
Authors: Darell E. Heiselman
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Callaham et al<sup>1</sup>state in their "Methods" section that informed consent was not obtained but was "implied on a compassionate basis." I can understand the need to enroll patients without consent into such a study because of the urgency of the clinical setting. In addition, the incurred delay in attempting to obtain informed consent from surrogate decision makers would make conclusions and effects of treatment impossible to interpret. Recently, there have been a multitude of reports involving resuscitation research using high-dose epinephrine.<sup>2,3</sup>Before we begin down this slippery slope, we as researchers in cardiopulmonary resuscitation must ensure that if there is to be no informed consent, ethically there at least must be disclosure of the research performed. My concern is that investigators in trials such as the one reported make no statements or assurances that truthful, full disclosure was performed, especially to the families of
Ready-Made, Recalibrated, or Remodeled?
Authors: Joan Ivanov, Jack V. Tu, C. David Naylor
Journal: Circulation (1999)

Background —Risk indexes for operative mortality after cardiac surgery are used for comparative profiling of surgeons or centers. We examined whether clinicians and managers should use an existing index without modification, recalibrate it for their populations, or derive a new model altogether. Methods and Results —Drawing on 7491 consecutive patients who underwent isolated CABG at 2 Toronto teaching hospitals between 1993 and 1996, we compared 3 strategies: (1) using a ready-made model originally derived and validated in our jurisdiction; (2) recalibrating the ready-made model to better fit the population; and (3) deriving a new model with additional risk factors. We assessed statistical accuracy, ie, area under a receiver-operator characteristic curve (ROC); precision, ie, statistical goodness-of-fit; and actual impact on both risk-adjusted operative mortalities (RAOM) and performance rankings for 14 surgeons. The new model was slightly more accurate than the ready-made model (ROC, 0.78 versus 0.76; P &lt;0.05), albeit not different from the recalibrated model (ROC, 0.77). The ready-made model showed poor fit between the predicted and observed results ( P &lt;0.001), leading to significant underestimation of RAOM (1.6±0.2%) compared with the other strategies (2.5±0.2%; P =0.048). Remodeling also changed the performance rankings among half the surgeons with higher RAOM. Conclusions —Poorly calibrated risk algorithms can bias the calculation of RAOM and alter the results of surgeon-specific profiles. Any existing index used for risk assessment in cardiac surgery should be episodically recalibrated or compared with new models derived from local subjects to ensure that its performance remains optimal.
POST-ANESTHETIC PARALYSES.
Authors: C. C. HERSMAN
Journal: JAMA (1901)

Paralyses following an anesthetic which are due to that agent alone are more imagined than real. Were it not for those unfamiliar with the recent literature on the subject it would seem an imposition to burden the profession to enter further into the discussion. "Anesthesia paralysis," post-operative paralysis," etc., still in use, foster erroneous conclusions and should be dispensed with. It is well known to neurologists that in many alcoholics, or other drug habitués, the vulnerability of a nerve trunk is so increased that a very moderate degree of pressure over it will produce a tingling or numbness, and slight injuries may even invite a neuritis. However, we could not seriously consider an acute toxemia as an etiological factor diminishing the resistance of peripheral nerves, rendering them more susceptible to a peripheral palsy as a sequence of general anesthesia. Seldom have I seen a post-anesthetic paralysis that did not clear
First Experience With Proteasome Inhibitor Treatment of Radioiodine Nonavid Thyroid Cancer Using Bortezomib
Authors: Daniel Putzer, Micheal Gabriel, Alexander Kroiss, Ruth Madleitner, Wolfgang Eisterer, Dorota Kendler, Christian Uprimny, Reto J. Bale, Günther Gastl, Irene J. Virgolini
Journal: Clinical Nuclear Medicine (2012)

Purpose Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a poor prognosis. Despite a multimodal therapeutic approach including surgery, chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a high number of TC-associated deaths. The aim of this investigation was to evaluate the response rate of progressive TC patients to treatment with the proteasome inhibitor bortezomib. Materials and Methods Seven patients with inoperable, metastasized progressive TC proven to be radioiodine nonavid were included into this pilot study. Patients received bortezomib intravenously with a standardized dose of 1.3 mg/m2 on days 1, 4, 8, and 11. All patients underwent 3 therapeutic cycles with an interval of 10 days. [18F]2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) and measurements of thyroglobulin levels were performed before, during, and after therapy, with a 6-week interval to post-therapeutic follow-up. Results Stable disease was seen after proteasome inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease of maximum standardized uptake value in both post-therapeutic follow-up investigations, and one of these cases also had decreasing thyroglobulin levels. Two patients experienced stable disease during the posttherapeutic follow-up. Two patients showing a mixed response had an improvement in their clinical situation. One patient had rapidly progressive disease, and died 3 months after the last therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and alterations of the blood count up to WHO (World Health Organization) grade 2 in 5 patients. Conclusion Proteasome inhibitor treatment with bortezomib is a promising therapeutic approach in TC patients without an established treatment alternative. The development of a specific therapeutic regimen for the treatment of radioiodine nonavid TC is warranted.
Exploring beyond cirrhosis
Authors: Massimo Pinzani, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Journal: Hepatology (2012)

“Cirrhosis” is a morphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus, document by the International Liver Pathology Study Group, challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment. (HEPATOLOGY 2012;)
latheo Encodes a Subunit of the Origin Recognition Complex and Disrupts Neuronal Proliferation and Adult Olfactory Memory When Mutant
Authors: Shirly Pinto, David G Quintana, Patrick Smith, Robert M Mihalek, Zhi-Hui Hou, Susan Boynton, Christopher J Jones, Marvin Hendricks, Klara Velinzon, James A Wohlschlegel, Richard J Austin, William S Lane, Tim Tully, Anindya Dutta
Journal: Neuron (1999)
Treatment of chronic urticaria
Authors: Robin Marks
Journal: British Journal of Dermatology (1980)

Journal Article Treatment of chronic urticaria Get access Robin Marks Robin Marks Department of Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 2, 1 February 1980, Page 240, https://doi.org/10.1111/j.1365-2133.1980.tb05702.x Published: 01 February 1980
DIFFUSE MESODERMAL PIGMENTATION WITH CONGENITAL CRANIAL ABNORMALITY
Authors: ALICE CARLETON, ROSEMARY BIGGS
Journal: British Journal of Dermatology (1948)

Journal Article DIFFUSE MESODERMAL PIGMENTATION WITH CONGENITAL CRANIAL ABNORMALITY Get access ALICE CARLETON, M.D., N.U.I., ALICE CARLETON, M.D., N.U.I. Physican in Charge of Dermatological Department Search for other works by this author on: Oxford Academic Google Scholar ROSEMARY BIGGS, M.B., B.S.Lond. ROSEMARY BIGGS, M.B., B.S.Lond. Assistant Pathologist, Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 60, Issue 1, 1 January 1948, Pages 10–13, https://doi.org/10.1111/j.1365-2133.1948.tb10925.x Published: 01 January 1948
Postural proteinuria and lipoid nephrosis of 58 years' duration.
Authors: M L Simenhoff
Journal: BMJ (1976)

atropine, and hyoscine and have been ingested, especially in the USA, for their hallucinogenic properties.Deaths have resulted.5Our patients ate Surama cigarettes, which contain 92-5% stramo- nium leaf (equivalent to 1-5-2-5 mg alkaloids per cigarette).They displayed many features typical of anticholinergic poisoning but re- covered without specific treatment.In severe poisoning physostigmine salicylate may be of value.The occurrence of two or possibly four cases in so short a time suggests that the potentially lethal practice of ingesting such cigarettes for kicks may be enjoying a vogue.We are grateful to Dr A T Proudfoot and Dr L F Prescott for permission to report details of patients under their care and
What is the impact of medical education in the early years?
Authors: Brendan S Fletcher
Journal: Journal of the Royal Society of Medicine (2009)

I read with interest Calvert et al.'s study from the University of Birmingham and was encouraged to read that graduate entry students are out-performing mainstream counterparts in medical school examinations in the later stages.1 Their discussion did allude to different teaching methods used in the first phase of the Birmingham course but did not suggest how much of a contribution this makes to performance in the second stage. They did not discuss how big the groups used for teaching were in both the graduate and mainstream programmes.

The results included 161 graduate entry and 1386 mainstream students. If class size is potentially a factor in early years education, might the Birmingham group consider looking at their own class sizes and assessing whether or not this might also be a factor in medical education? If Birmingham is educating graduates in its mainstream programme, it may be interesting to see how these students perform in relation to their graduate course peers. In addition, might it be possible for school-leavers to be educated in the graduate entry programme for phase 1, to act as a comparison?

Presumably, when there are two different models for delivering the early years of medical education in the same medical school, there must be a reason for this and one wonders why it is not considered appropriate to apply the graduate course model to mainstream programmes.

When people who entered medical school as school-leavers read sentences such as: ‘Graduate entry students are generally more mature than non-graduate entry students’ it may get their heckles up, so I was particularly pleased to read that the Birmingham group did not suggest that graduate entry students make ‘better’ doctors on the basis of good exam results.
Increased interleukin 6 and Tissue factor production during dobutamine stress echocardiography is associated with ischemia and left ventricular dyfunction
Authors: Ignatios Ikonomidis, George Athanassopoulos, John Lekakis, Kiriaki Venetsanou, Margarita Marinou, Petros Nihoyannopoulos, Dennis Cokkinos, Stamatios Stamatelopoulos
Journal: Journal of the American College of Cardiology (2003)
Esophagitis dissecans: a rare cause of odynophagia
Authors: N. Patel, C. Salathé, C. Vu, S. Anderson
Journal: Endoscopy (2007)

A 67-year-old woman with Sjögren’s syndrome, IgA paraproteinemia, and bronchiectasis presented with a 3-month history of worsening odynophagia and weight loss. Initial endoscopy revealed erythema in the mid- to distal esophagus and a small mucosal tear. Barium swallow, esophageal manometry, and 24-hour pH studies were all normal. Her symptoms worsened despite proton-pump inhibitor therapy. Repeat endoscopy showed denuded mucosa with overlying slough in the mid-esophagus ([Figure 1]) and a superficial bulla ([Figure 2]). The patient had no mucocutaneous lesions and an empirical trial of oral corticosteroids was ineffective. Esophageal biopsies showed ulcerated and inflamed squamous mucosa ([Figure 3]), but indirect immunofluorescence studies were negative. Fungal hyphae were noted but antifungal therapy was unsuccessful. All routine and autoimmune-screen blood tests were essentially normal. She later developed generalized lymphadenopathy and diffuse large B-cell lymphoma was diagnosed. Treatment with rituximab (anti-CD 20) resulted in a rapid improvement in her dysphagia, and subsequent endoscopy showed normal mucosa with a fibrotic esophageal stricture, which was dilated ([Figure 4]). Biopsies showed only mild, nonspecific inflammation and no malignancy.
Blockade of endothelin receptors markedly reduces atherosclerosis in LDL receptor deficient mice: role of endothelin in macrophage foam cell formation
Authors: S Babaei
Journal: Cardiovascular Research (2000)

Objective: We evaluated the direct effects of long-term blockade of ETA and ETB receptors using a mixed endothelin (ET) receptor antagonist, LU224332, in the low density lipoprotein receptor (LDL-R) knockout mouse model of atherosclerosis. Methods: Four groups of LDL-R deficient mice were studied: control mice fed normal chow (group I); mice fed a high cholesterol (HC, 1.25%) diet alone (group II), HC fed animals treated with LU224332 (group III); and mice fed normal chow treated with the LU compound (group IV). All treatments were continued for 8 weeks at which time the animals were sacrificed and the aortae were removed and stained with oil red O. Atherosclerotic area (AA) was determined by quantitative morphometry and normalized relative to total aortic area (TA). Results: Cholesterol feeding resulted in a marked increased in total plasma cholesterol (∼15 fold) and widespread aortic atherosclerosis (AA/TA: group I: 0.013±0.007; group II: 0.33±0.11; P<0.001). Atherosclerotic lesions were characterized by immunohistochemistry as consisting mainly of macrophages which also showed high levels of ET-1 expression. Treatment with ET antagonist significantly reduced the development of atherosclerosis (AA/TA: group III: 0.19±0.07, P<0.01 vs. group II), without altering plasma cholesterol levels and blood pressure. The direct effect of LU224332 on macrophage activation and foam-cell formation was determined in vitro using a human macrophage cell line, THP-1. Treatment of the THP-1 cells with LU224332 significantly reduced cholesterol ester and triacylglycerol accumulation and foam-cell formation on exposure to oxidized LDL (P<0.01 and P<0.05, respectively). Conclusion: We conclude that a nonselective ET receptor antagonist substantially inhibited the development of atherosclerosis in a genetic model of hyperlipidemia, possibly by inhibiting macrophage foam-cell formation, suggesting a role for these agents in the treatment and prevention of atherosclerotic vascular disease.
Stress Buffering and Glycemic Control: The Role of Coping Styles
Authors: Mark F Peyrot, James F McMurry
Journal: Diabetes Care (1992)

To test the hypotheses that chronic psychosocial stress is associated with worse glycemic control and that coping moderates (buffers) this effect.Subjects consisted of 105 insulin-treated adults from the Diabetes Division of Henry Ford Hospital who filled out questionnaires on stress and coping and received an HbA1 test at a clinic appointment. Six coping styles were examined, including both emotion- and problem-focused styles. Two standardized stress inventories were administered. Ineffective coping was defined as scoring below the median for stress-dampening coping styles and above the median for stress-exacerbating styles.Stress was significantly (P less than 0.05) correlated with higher HbA1 in all but one ineffective coping subgroup. Conversely, none of 12 correlations between stress and glycemic control was significant in the effective coping subgroups.Chronic psychosocial stress is associated with worse glycemic control among those who do not cope effectively with stress. Effective coping can protect individuals from the deleterious effects of stress.
Coactivator SRC-2–dependent metabolic reprogramming mediates prostate cancer survival and metastasis
Authors: Subhamoy Dasgupta, Nagireddy Putluri, Weiwen Long, Bin Zhang, Jianghua Wang, Akash K. Kaushik, James M. Arnold, Salil K. Bhowmik, Erin Stashi, Christine A. Brennan, Kimal Rajapakshe, Cristian Coarfa, Nicholas Mitsiades, Michael M. Ittmann, Arul M. Chinnaiyan, Arun Sreekumar, Bert W. O’Malley
Journal: Journal of Clinical Investigation (2015)

Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2–driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.