tbuckley/cabot-search huggingface dataset:
Levadopa and pyridoxine
Authors: H. Mars
Journal: JAMA (1972)

To the Editor.—  Recent reports inThe Journalhave clearly indicated the negative effects of pyridoxine on the therapeutic response of patients with parkinsonism to levodopa.1,2Blood dopa levels have been demonstrated as decreased and clinical disability augmented following co-administration of dopa and pyridoxine. It is believed that these responses are due to an activation of systemic dopa decarboxylation by the vitamin. Cotzias et al3have theorized and presented supportive clinical data that, under conditions of peripheral decarboxylase inhibition, as produced by the inhibitor α-methyldopa hydrazine (MK-486), the antagonistic actions of pyridoxine to dopa effect are reversed. Enhancement may result, as evidenced by lower daily dopa requirements and sudden onset of toxic effects.  In order to investigate this effect further, mice were injected intraperitoneally with placebo, levodopa (100 mg/kg), MK-486, (50 mg/kg), and pyridoxal-5-phosphate, (5 mg/kg), singly or in combination. One hour later, the animals were killed, and
Response to Letter Regarding Article, “The Global Cardiovascular Risk Transition: Associations of Four Metabolic Risk Factors With Macroeconomic Variables in 1980 and 2008”
Authors: Goodarz Danaei, Gitanjali M. Singh, Christopher J. Paciorek, John K. Lin, Melanie J. Cowan, Mariel M. Finucane, Farshad Farzadfar, Gretchen A. Stevens, Leanne M. Riley, Yuan Lu, Mayuree Rao, Majid Ezzati
Journal: Circulation (2013)
Abstract 989: Mild ER stress increases human ABC transporter expression and drug transport function in polarized cell monolayers.
Authors: King Leung Fung, Jessica Pixley, Darrell J. Talbert, Khyati Kapoor, Suresh Ambudkar, Michael M. Gottesman
Journal: Cancer Research (2013)

Abstract Expression of ATP-binding cassette (ABC) transporter genes such as MDR1 (ABCB1/P-gp) is associated with poor outcome in chemotherapy and a multidrug resistant phenotype in cancer. Endoplasmic reticulum (ER) stress has been implicated in tumor growth but its role in drug resistance remains unclear. Here, we hypothesize that ER stress could increase expression of drug efflux transporters. To test this hypothesis, we developed a transient expression system in which human ABC transporters were ectopically expressed in a cell line monolayer by the BacMam baculovirus. The baculovirus is able to infect several mammalian cell lines including LLC-PK1, T-84, and MA104 without affecting the tightness of the host cell monolayers. In LLC-PK1 cells infected by BacMam vectors, induction of mild ER stress by pre-incubation (pre-conditioning) with thapsigargin (0.5 μg/ml) or tunicamycin (1 μg/ml), which are well-characterized ER-stress inducers, increased ABCB1 (P-gp) and ABCG2 (BCRP) levels. Drug transport assays showed that P-gp expressing cells pre-conditioned with thapsigargin showed increased directional transport of [3H] paclitaxel across the cell monolayer. The effect of thapsigargin was inhibited by the presence of the Erk inhibitor PD098059 but not the P38(MAPK) inhibitor SB203580, or the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002, suggesting that expression of ABC transporter is influenced by mild ER stress response and, at least in part, by the ERK/MAPK signaling pathway. Although pre-conditioning with tunicamycin can increase P-gp expression, it also inhibits N-glycosylation of P-gp. Collectively, our findings indicate that mild ER stress responses up-regulate drug transporters introduced into cells by BacMam vectors. Citation Format: King Leung Fung, Jessica Pixley, Darrell J. Talbert, Khyati Kapoor, Suresh Ambudkar, Michael M. Gottesman. Mild ER stress increases human ABC transporter expression and drug transport function in polarized cell monolayers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 989. doi:10.1158/1538-7445.AM2013-989
Sudden Onset of Headache, Proptosis, and Roaring Tinnitus in a Hypertensive 60-Year-Old Woman
Authors: Eric J. Russell, Michael Huckman, Michael Rosenberg
Journal: JAMA (1983)

<h3>History</h3> A mildly hypertensive 60-year-old woman experienced an acute throbbing right frontal headache, right partial ptosis, and an audible roar centered at the right ear. During the next 12 hours, the eye became red and proptotic and finally closed. The patient gave no history of trauma. On physical examination, BP was 120/70 mm Hg and the pulse rate was 60 beats per minute and regular. Vision was normal in the right eye, but ptosis, subconjunctival hemorrhage, and chemosis were present. The right pupil was dilated and nonreactive to light. A complete third-nerve palsy was noted. Ophthalmoscopic examination gave normal findings. A roaring bruit was heard over the right side of the skull; it was best heard at the right orbit. Cerebral angiography was performed on the day of admission (Fig 1, top and bottom left), and definitive treatment was instituted six days later. <h3>Diagnosis</h3> Spontaneous carotid-cavernous fistula. The diagnosis was
Underutilization of Aspirin Persists in US Ambulatory Care for the Secondary and Primary Prevention of Cardiovascular Disease
Authors: Randall S Stafford, Veronica Monti, Jun Ma
Journal: PLoS Medicine (2005)

Despite the proven benefits of aspirin therapy in the primary and secondary prevention of cardiovascular disease (CVD), utilization rates of aspirin remain suboptimal in relation to recommendations. We studied national trends of aspirin use among intermediate- to high-risk patients in the US ambulatory care settings and compared the priority given to aspirin versus statins for CVD risk reduction. We also examined patient and health care provider contributors to the underuse of aspirin.
Some considerations concerning multimedia-multipollutant risk assessment methodology: use of epidemiologic data for non-cancer risk assessment in Russia.
Authors: L I Privalova, K E Wilcock, B A Katsnelson, S E Keane, K Cunningham, S V Kuzmin, S A Voronin, B I Nikonov, V B Gurvich
Journal: Environmental Health Perspectives (2001)

The highly industrialized small town of Verkhnyaya Pyshma (in the Urals region of Russia) was chosen as the site of a multimedia-multipollutant risk assessment using the U.S. Environmental Protection Agency methodology. The assessment was based on routine environmental pollution monitoring data for ambient air, soils, drinking water, and food, and the international environmental epidemiology literature. Using an a priori set of the preliminary health-based criteria, we selected nine pollutants for risk assessment: total suspended particles (TSP), sulfur dioxide, nitrogen dioxide, benzo(a)pyrene (BaP), ammonia arsenic, copper, cadmium, and lead. We used dose-response functions derived from epidemiologic studies to assess individual and population risks for TSP, SO2, NO2, As, Cd, and Pb. We assessed both cancer (for BaP, As, and Cd) and non-cancer (for all the chosen pollutants but BaP) responses, but in this paper we discuss only the assessments of noncarcinogenic risks due to TSP, SO2, NO2, Pb, and Cd as examples of how the quantitative estimates of health effects can be produced by using a risk function approach. We also schematically present a modified conceptual model of multimedia-multipollutant risk assessment taking into account the experience gained with this study.
The Renaissance in HIV Vaccine Development — Future Directions
Authors: Wayne C. Koff, Seth F. Berkley
Journal: New England Journal of Medicine (2010)

From July 18 through July 23, 2010, delegates from around the globe will convene for the biennial International AIDS Conference in Vienna. They will discuss our current risk of losing the war against the human immunodeficiency virus (HIV). Despite an unprecedented outpouring of resources and proliferation of programs, today, for every two patients who begin receiving treatment for HIV, five people are newly infected. Furthermore, new guidelines from the World Health Organization recommending that infected persons begin receiving treatment earlier will significantly increase the number of patients targeted for therapy. If we are to control this pandemic, we must recognize . . .
Diagnostic criteria for acute myocardial infarction in patients undergoing coronary artery bypass surgery.
Authors: D S Raabe, A Morise, J A Sbarbaro, W D Gundel
Journal: Circulation (1980)

Current techniques for diagnosing perioperative myocardial infarction were studied in 58 patients who underwent coronary bypass surgery. All patients had preoperative and postoperative ECGs and technetium-99m stannous pyrophosphate myocardial scintigrams; serum CK-MB was measured immediately after surgery and daily for 3 days. Postoperative bypass graft visualization and left ventriculography were performed before hospital discharge in every patient. Nine patients (16%) had new Q waves postoperatively. Five of these nine patients had positive pyrophosphate scintigrams, postive CK-MB and new wall motion abnormalities, and the remaining four had negative CK-MB, negative phyrophosphate scintigrams and no new wall motion abnormalities. Seven patients (12%) had newly positive postoperative pyrophosphate scintigrams, positive CK-MB and new wall motion abnormalities on postoperative ventriculography, but only four had new Q waves postoperatively. Eight patients (14%) had new wall motion abnormalities; seven had positive pyrophosphate scintigrams and all had positive CK-MB, but only five had new Q waves. Sixteen patients (28%) had positive CK-MB, including all patients with either positive pyrophosphate scintigrams or new wall motion abnormalities, Eight patients had positive CK-MB without other evidence of perioperative infarction. A newly positive postoperative pyrophosphate scintigram is more senstive and specific than the development of new postoperative Q waves for the diagnosis of hemodynamically significatn perioperative myocardial in farction. CK-MB is highly sensitive, but too nonspecific to be useful for the diagnosis of perioperative infarction.
Ischemic Colitis: Tc-99m HMPAO Leukocyte Scintigraphy and Correlative Imaging
Authors: HYEWON HYUN, EUGENE PAI, MICHAEL J. BLEND
Journal: Clinical Nuclear Medicine (1998)

A 62-year-old woman became progressively ill after aorto-bifemoral graft surgery. A Tc-99m hexamethylpropyleneamine oxime (HMPAO) leukocyte scan was performed because of fever and suspected graft infection. The anterior abdominal and pelvic views demonstrated marked uptake within the sigmoid colon. Follow-up studies, including CT scan and contrast intestinal x-rays, confirmed the presence of an abnormal sigmoid loop. Subsequent surgical resection and pathological examination of the sigmoid colon revealed ischemic changes. To our knowledge, detection of ischemic colitis using Tc-99m HMPAO labeled leukocytes has not been reported. Clinical and routine radiological findings of ischemic colitis are typically nonspecific and may result in delayed diagnosis that can lead to high mortality. Tc-99m HMPAO leukocyte scintigraphy may be helpful in the noninvasive diagnosis of ischemic injury to the colon, especially after aortic graft surgery.
Ewart Geoffrey Walsh
Authors: Robert A Minns, M Lakie
Journal: BMJ (2003)

Geoffrey Walsh undertook ingenious physiological measurements on human subjects to study the sensory nervous system or understand motor control problems in children with cerebral palsy and adults with multiple sclerosis. Often he used apparatus that he designed and constructed himself.​himself.




Figure 1




After clinical appointments Dr Walsh obtained his MRCP in 1950 and was appointed lecturer in physiology at Edinburgh University, where he remained for the rest of his career, subsequently becoming senior lecturer and reader. He was an internationally acclaimed expert on the physiology of the human nervous system, lecturing at universities worldwide, and he published more than 150 scientific papers on human neurophysiology, biomechanics, and clinical physiology. His first book, Physiology of the Nervous System, was a classic.

A major innovation was his measurement of muscle tone by the assessment of resonating frequency and his demonstration that muscles behaved thixotropically, sometimes like a solid and sometimes, when shaken or stirred, like a liquid—a bit like tomato ketchup. This was a unique system, which remains the only objective measurement of muscle tone. His book Muscles, Masses and Motion: The Physiology of Normality, Hypotonicity, Spasticity and Rigidity was published in 1992. This represented a compendium of current knowledge about posture control in normal people, including medical students and Buddhist monks, and in those with special skills such as sportsmen and musicians, and in children with cerebral palsy. He was latterly involved in biomechanical research investigating “shaken baby syndrome.”

Geoffrey lived for neurophysiology experiments and Edinburgh medical students and staff remember being recruited as volunteers for yet another study on complex finger movements or tests of vestibular function.

He leaves three daughters and their families.

Ewart Geoffrey Walsh, former reader in physiology Edinburgh University (b Cheltenham 1922; q Oxford 1947; MD (Harvard), FRCP, FRCP Ed, FRS Ed), d 26 March 2003.
Bad medicine: depression
Authors: D. Spence
Journal: BMJ (2010)

A fundamental question for society is: while we have become richer and healthier, why have we become unhappier? Self reported depression has risen steadily, and a leading charity claims that one in 10 of us is currently depressed and that the lifetime risk is one in four. Such figures have been splashed across the media, and depression is presented as a particular problem in young people, with a rising rate of self harm in this group. Medical pundits still claim that depression is underdiagnosed and undertreated. We have a …
Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.
Authors: B L Riser, P Cortes, X Zhao, J Bernstein, F Dumler, R G Narins
Journal: Journal of Clinical Investigation (1992)

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.
FGF-2 and VEGF functionalization of starPEG–heparin hydrogels to modulate biomolecular and physical cues of angiogenesis
Authors: Andrea Zieris, Silvana Prokoph, Kandice R. Levental, Petra B. Welzel, Milauscha Grimmer, Uwe Freudenberg, Carsten Werner
Journal: Biomaterials (2010)
Randomized Trials or Observational Tribulations?
Authors: Stuart J. Pocock, Diana R. Elbourne
Journal: New England Journal of Medicine (2000)

The role of observational studies in the evaluation of treatments is a long-standing and contentious topic.1 In this issue of the Journal, Concato et al.2 and Benson and Hartz3 report that observational studies give results similar to those of randomized, controlled trials. If these claims lead to more observational studies of therapeutic interventions and fewer randomized, controlled trials, we see considerable dangers to clinical research and even to the well-being of patients.Any systematic review of evidence on a therapeutic topic needs to take into account the quality of the evidence. Any study, whether randomized or observational, may have flaws . . .
Abstract P2-10-02: Clinical validation of the PAM50 risk of recurrence (ROR) score for predicting residual risk of distant-recurrence (DR) after endocrine therapy in postmenopausal women with ER+ early breast cancer (EBC): An ABCSG study
Authors: M Gnant, M Filipits, B Mlineritsch, P Dubsky, R Jakesz, W Kwasny, F Fitzal, M Rudas, M Knauer, C Singer, R Greil, S Ferree, J Storhoff, JW Cowens, C Schaper, S Liu, T Nielsen
Journal: Cancer Research (2012)

Abstract Aim: To assess the performance of the ROR score in predicting DR for postmenopausal patients with ER+ EBC treated with tamoxifen or tamoxifen followed by anastrozole when the PAM50 test is performed in a routine hospital pathology laboratory. Background: The multi-analyte gene-expression tests (Oncotype DX, MammaPrint) that are currently used in clinical practice to assess prognosis after endocrine therapy in primary ER+ breast cancer are performed in a central referral laboratory. PAM50 is a 50-gene test in development that is designed to be performed in local routine hospital pathology laboratories and has been optimized to separate intrinsic disease subtypes which are used to generate a ROR score. This ROR score has been clinically validated and demonstrated to contain more prognostic information than Oncotype Dx RS in the TransATAC patient population (Dowsett, SABCS, 2011). Methods: 1,251 women from the prospective randomized ABCSG-8 trial were entered into this study: the entry criteria were the availability of their FPET block and informed consent. Three unstained 10 micron sections and 1 H&amp;E slide for each patient were sent to an independent academic pathology laboratory at BCCA where tissue review, manual micro-dissection and RNA extraction were performed. PAM50 analysis was then conducted on 250 ng of the extracted RNA using the NanoString nCounter® technology: both intrinsic subtype and ROR score were calculated. The median follow up of the patients entered into this study is 10 years. 912 are node negative and 339 are node positive. The baseline characteristics of the patients entered showed them to be a representative sample of the overall ABCSG-8 trial population. The primary analysis is designed to test whether the continuous ROR score adds prognostic value over and above the standard clinical variables, using a likelihood ratio test. Results: Results are currently being derived and will be presented in full at SABCS. Discussion: This large clinical trial serves both as a clinical validation study of the PAM 50 test and as a demonstration that a complex multi-analyte gene-expression test can be performed in a routine hospital pathology laboratory while meeting the same quality metrics as a central referral laboratory. The results of the primary analysis, when combined with the results already reported from the Trans ATAC population, yield Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC and form the basis of the design of the clinical utility studies of the PAM 50 test. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-02.
Hypothermia: a complication of diabetic ketoacidosis.
Authors: E A Gale, R B Tattersall
Journal: BMJ (1978)

During 1969-77, 20 episodes of severe hypothermia occurred in 19 diabetic patients in Nottingham. Thirteen were associated with ketotic hyperosmolar coma, two with lactic acidosis, and one with hypoglycaemia, while in four there was no loss of diabetic control. Ketoacidosis accounted for 11.8% of all admissions for severe accidental hypothermia and was a commoner cause than hypothyroidism (8%). Patients with ketoacidosis were younger and developed hypothermia as often during the summer as during the winter. The metabolic disturbance was characteristic, with severe acidosis (mean pH 7.04), a high blood glucose concentration (mean 56.6 mmol/l; 1020 mg/100 ml), and high plasma osmolality (mean 379.7 mmol (mosmol)/kg). Eight of the 13 episodes proved fatal. Hypothermia may aggravate ketoacidosis and complicate treatment and should be sought in all patients with severe diabetic coma.
Low incidence of osteoarthrosis in hip and knee after anterior poliomyelitis: a late review.
Authors: J. H. Glyn, I. Sutherland, G. F. Walker, A. C. Young
Journal: BMJ (1966)

Low-molecular-weight Dextran-Morgan et al.MBoRf 739 is much less certainly established.While dramatic early improvement has been seen many times, the long-term results have been disappointing.We do not think that a definite advantage will be shown over the results that can be obtained with intravenous heparin drips.FIG. 4. Typical renal biopsy appearance.Note distension and vacuola- non of renal tubular cells and marked reduction of tubular lumen.(Haematoxylin and eosin.x 110.) SummaryThree cases of profound oliguria following courses of low- molecular-weight dextran are reported.Two patients had generalized vascular disease but no other evidence of renal involvement.All were given adequate fluids during treatment and none suffered episodes of hypotension.Renal biopsy material was obtained from each case, and a florid form of " osmotic nephrosis " was noted in each.There was no evidence that oliguria was due to intraluminal aggregations of dextran; rather it seemed that either luminal compromise by greatly distended tubular cells or cellular impairment by contained dextran was responsible.The value of low-molecularweight dextran in such cases is uncertain, but it is obvious that prolonged courses should be employed with the utmost caution if they are to be used at all.