tbuckley/cabot-search huggingface dataset:
Bone marrow trephine biopsy findings in primary myelofibrosis
Authors: Kikkeri N. Naresh
Journal: American Journal of Hematology (2010)

1 A man in 50s presented with anemia and elevated white cell count. His hemoglobin was 9.7 g/dL and white cell count was 19.3 × 109/L, with neutrophils amounting to 13.2 × 109/L. His platelets measured 64 × 109/L. Peripheral blood evaluation showed numerous tear-drop cells and a leukoerythroblastic appearance (a). The bone marrow trephine biopsy showed hypercellular marrow and thick irregular bony trabeculae (osteosclerosis) (b). There were dilated sinuses with areas of intrasinusoidal hematopoiesis. The megakaryocytes were increased in number. They were seen in clusters and there was wide variation in their size and nuclear lobation. Large megakaryocytes and cells with hyperchromatic nuclei were also noted (c and d). CD34 immunostain showed no excess of precursor cells but highlighted intrasinusoidal hematopoiesis (e). CD42b immunostain (f) highlighted the abnormal megakaryocytes and myeloperoxidase immunostain (g) highlighted dominance of myeloid lineage cells in some of the fragments. The reticulin stain (h) highlighted diffuse increase in coarse reticulin fibers and focal presence of collagen, which stained brown. The marrow reticulin was graded as MF-2. In addition, there was evidence of V617F mutation in the JAK2 gene. The case represents primary myelofibrosis (PMF), where the marrow is still cellular. PMF is a clonal myeloproliferative neoplasm. Peripheral blood typically shows leukoerythroblastosis and anisopoikilocytosis. Constitutional symptoms, anemia, leukocytosis, and thrombocytosis, are frequent presenting features. Splenomegaly is seen in a majority of patients, and hepatomegaly is also frequent. In the early stages of PMF, the bone marrow is mostly hypercellular with prominence of myeloid lineage cells, which are left-sifted. Megakaryocytes are markedly abnormal with frequent presence of large cells with hyperchromatic or hyperlobated nuclei. JAK2-V617F mutation is seen in ∼50% patients. A systematic approach is essential for the diagnosis of these bone marrow trephine biopsies [1]. Diagnosis and classification of early stages of myeloproliferative neoplasms is challenging and has been addressed in a recent review [2].
Long term metabolic effects of two dietary methods of treating hyperlipidaemia
Authors: A A Rivellese, P Auletta, G Marotta, G Saldalamacchia, A Giacoo, V Mastrilli, O Vaccaro, G Riccardi
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objectives</b> : To compare the long term metabolic effects of two diets for treating hyperlipidaemia. <b>Design</b> : Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. <b>Setting</b> : Lipid clinic of tertiary referral centre in Naples. <b>Subjects</b> : 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. <b>Interventions</b> : Two test diets with reduced saturated fat (8%) and cholesterol (-200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. <b>Main outcome measures</b> : Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. <b>Results</b> : In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/1, P&lt;0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P&lt;0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P&lt;0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P&lt;0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. <b>Conclusions</b> : Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.
GENERAL PHYSIOLOGY OF THE ANTERIOR HYPOPHYSIS
Authors: PHILIP E. SMITH
Journal: JAMA (1935)

<h3>Note.—</h3> <i>These articles and those in</i>The Journal<i>last week are part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues of</i>The Journal.—Ed. Although the general physiology of the anterior hypophysis is inseparable from its special physiology, a general discussion of the recent developments of our knowledge of pituitary physiology may be of value. Experimental and other work is increasingly showing the important position which this organ occupies among the endocrine glands. There appear to be but few body functions that it does not influence, either directly or indirectly. Barger has spoken of it as "general headquarters" of the endocrine system, a characterization that aptly expresses its dominant position in this system. Undoubtedly, the large number of contributions that have been published on the anterior hypophysis within the last decade have not simplified
(3) Recurrent cutaneous suppuration complicating acne with paroxysmal nocturnal haemoglobinuria (PNH)
Authors: P.J.A. Holt, G.A. Hodgson
Journal: British Journal of Dermatology (1973)

Journal Article (3) Recurrent cutaneous suppuration complicating acne with paroxysmal nocturnal haemoglobinuria (PNH) Get access P.J.A. Holt, P.J.A. Holt Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar G.A. Hodgson G.A. Hodgson Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 29–32, https://doi.org/10.1111/j.1365-2133.1973.tb03436.x Published: 01 July 1973
Ca,Mg-ATPase activity of permeabilised rat heart cells and its functional coupling to oxidative phosphorylation of the cells
Authors: L. KUMMEL
Journal: Cardiovascular Research (1988)

Journal Article Ca,Mg-ATPase activity of permeabilised rat heart cells and its functional coupling to oxidative phosphorylation of the cells Get access LADISLAV KÜMMEL LADISLAV KÜMMEL From the Laboratory for Endocrinology and Metabolism, Charles University, Faculty of Medicine, Prague, Czechoslovakia; and the Department of Medicine, Cardiovascular Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 5, May 1988, Pages 359–367, https://doi.org/10.1093/cvr/22.5.359 Published: 01 May 1988 Article history Received: 16 September 1987 Accepted: 09 January 1988 Published: 01 May 1988
Malignant carcinoid tumour of the oesophagus.
Authors: A R Ready, J O Soul, J Newman, H R Matthews
Journal: Thorax (1989)

A patient with a carcinoid tumour of the oesophagus developed widespread metastases within three years of a successful local resection. Of the seven patients with oesophageal carcinoid tumours so far reported, four have died with widespread metastases.
Reducing Dietary Intake of Fat and Cholesterol in Children-Reply
Authors: Russell V. Luepker
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Olson, Dr Zlotkin, and Drs Newman and Hulley agree about the importance of blood cholesterol in atherosclerosis; however, they suggest it is a problem of adults, not a problem in children. Specifically, they question the magnitude of cholesterol lowering and costs of the DISC intervention,<sup>1</sup>the unknown safety among those not included in the trial, the association of fatty streaks observed in youth with more advanced lesions, and the relevance of diet among youth to adult eating patterns. While there are published data available to respond to each of these challenges, I will focus on their central implications: the current US diet for children is fine, there is no need to be concerned about cholesterol among youth, and we can wait until they become adults and approach the clinical disease threshold. In essence, they suggest that there is no role for cardiovascular disease prevention in a
Abstract 1439: Periostin expression is altered by TGF and hypoxia during breast cancer progression.
Authors: Michelle Coleman, Amanda Lance, Krista Ricci, Adam Secrest, Didier Dréau
Journal: Cancer Research (2013)

Abstract The extracellular matrix (ECM) contributes to the generation of normal breast tissue, and variations in the composition of the ECM have been shown to directly influence the formation and organization of acinus-like and duct-like structures. Specific ECM proteins are also important in the progression of several human cancers, and in particular upregulation of the ECM protein periostin has been linked to poor outcomes in breast cancer. Here we investigated the expression of periostin in biopsy specimens collected from breast cancer patients, as well as determined the differential effects of TGFß and hypoxia on the expression of periostin mRNA and protein in human breast cancer cells. Immunohistological analyses of the breast cancer biopsy specimens indicate that breast cancer tissues expressed different levels of periostin regardless of the stage of the disease and that the expression of periostin tended to decrease as breast cancer progressed. Multiple splice variants of periostin mRNA were expressed by breast cancer cells as determined by RT-PCR. Furthermore, treatments with either TGFß or hypoxia led to significantly different expression of periostin mRNA isoforms and of total level of periostin protein (p&amp;lt;0.05) by breast tumor cells. These observations support the role of periostin in breast cancer progression and suggest a role for specific periostin isoforms in response to changes in the microenvironment including tissue hypoxia and TGFß paracrine signaling from mesenchymal and immune cells. [This works is supported by grants from the Department of Defense Era of Hope research program (BC044778) and the National Science Foundation EFRI program (CBE0736007)] Citation Format: Michelle Coleman, Amanda Lance, Krista Ricci, Adam Secrest, Didier Dréau. Periostin expression is altered by TGF and hypoxia during breast cancer progression. [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 1439. doi:10.1158/1538-7445.AM2013-1439
Fungal nail infection: diagnosis and management
Authors: S. Eisman, R. Sinclair
Journal: BMJ (2014)

Pharmacokinetics of caffeine have been studied in sheep and cattle treated with caffeine (5 mg/kg) by intravenous injection. Terminal-phase elimination half-lives were 8.9 hr in sheep and 8.1 hr in cattle. Noncompartmental analyses of data collected from individual animals indicate that neither terminal-phase rate constants (beta) nor mean residence times of caffeine in plasma differed between species. Each of the three possible N-demethylated primary metabolites of caffeine was detected in plasma from each species, with theophylline predominating in sheep and paraxanthine predominating in cattle. These data indicate that hepatic capacity to clear caffeine from the systemic circulation is similar between sheep and cattle, but that the preferred routes of metabolism differ. Expression of cytochromes P4501A (CYP1A subfamily) may differ between these species.
Prostaglandin D2-induced bronchoconstriction is mediated only in part by the thromboxane prostanoid receptor
Authors: SL Johnston, NJ Freezer, W Ritter, S O'Toole, PH Howarth
Journal: European Respiratory Journal (1995)

Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the pathogenesis of asthma. PGD2 causes vasodilation acting via the prostaglandin (DP) receptor on vascular smooth muscle, and myocontraction acting via the thromboxane (TP) receptor on bronchial smooth muscle. To determine the relative contribution of these mechanisms we have studied the degree to which a potent TP receptor antagonist inhibits PGD2-induced bronchoconstriction. Twelve atopic asthmatic subjects underwent baseline PGD2 bronchial challenges to determine the cumulative concentration of PGD2 required to reduce forced expiratory volume in one second (FEV1) by 20%. At four subsequent randomized visits, subjects received this concentration of PGD2 90 min after dosing with placebo or 20, 50 or 100 mg of BAY u 3405, a potent competitive TP receptor antagonist. Serum was taken for drug assay at 90 min. After each dose of PGD2, FEV1 was measured for 30 min, and the area under the percentage fall in the FEV1/time curve (AUC) was calculated. The mean +/- SEM AUC for placebo was 414 +/- 68, and for the 20, 50 and 100 mg doses of BAY u 3405 was 169 +/- 33, 173 +/- 59 and 135 +/- 63, respectively. There were no significant differences between the AUCs for any of the drug doses, whilst all three doses were significantly different from placebo. The plateau response achieved with increasing doses of the antagonist suggests complete blockade of the TP receptor. These data demonstrate that thromboxane receptor blockade only partially inhibits the airway narrowing response to PGD2, and support the existence of a vascular component to PGD2-induced acute airway narrowing in asthma.
Insulin Treatment for the Early 80s: Facts and Questions About Old and New Insulins and Their Usage
Authors: John A Galloway
Journal: Diabetes Care (1980)

Recent data now emphasize the importance of blood glucose control as a means of forestalling diabetic microvascular disease. As a result, attempts are being made to optimize conventional insulin therapy, and new modes of insulin delivery (e.g., pumps) are being adopted. Also, improvements in manufacturing technology have resulted in the commercial availability of porcine insulin, which is highly effective in preventing the complications of insulin therapy in those patients receiving only this material. Human insulin, produced biosynthetically in bacteria using recombinant DNA technology, is now being tested. While these developments in insulin and its administration offer great promise to the diabetic patient, many more studies will be needed to determine their absolute clinical benefits.
A Double-modulation Strategy in Cancer Treatment With a Chemotherapeutic Agent and siRNA
Authors: Kazuya Nakamura, Amr S Abu Lila, Mariko Matsunaga, Yusuke Doi, Tatsuhiro Ishida, Hiroshi Kiwada
Journal: Molecular Therapy (2011)

5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors.
Latest figures show reduction in hospital admissions for stab wounds
Authors: O. Mashta
Journal: BMJ (2009)

Somatic symptom disorder (SSD) is characterised by a dysfunctional preoccupation with one or more physical symptoms. Patients with SSD often pursue excessive and unnecessary investigations, hospitalisations and treatments that significantly affect quality of life and drain healthcare resources. Thus, appropriate diagnosis and careful management are required to mitigate the patient9s distress and to reduce the burden to the healthcare system. SSD is a new disorder defined in the Diagnostic and Statistical Manual Fifth Edition (DSM-5), replacing somatoform and related disorders in the DSM-4-Text Revision with diagnostic criteria that are inclusive of a broad array of presentations. This report presents a detailed clinical case of an elderly man with a history of frequent hospital visits presenting with SSD. We discuss diagnostic challenges and evidence-based management in acute inpatient as well as in outpatient settings. We also review data on healthcare utilisation associated with SSD.
Use of Entonox in the Ambulance Service
Authors: P. J. F. Baskett, A. Withnell
Journal: BMJ (1970)

An analgesic mixture of nitrous oxide and oxygen (Entonox) has been used in nine ambulances in Gloucestershire for self-administration by patients in severe pain. Over a period of three and a half months 66 patients have been treated. In all cases the pain was wholly or partially relieved, and in no instance was the patient's condition worsened. No undesirable side-effects attributable to Entonox were produced. It is recommended that other ambulance authorities should consider the use of Entonox in this context.
Early Treatment of Upper Face Wounds
Authors: M. C. Oldfield
Journal: BMJ (1943)

DISEASES MEDICALTISOURNAL163 hospital with a joint laboratory, for public health bacteriology need not be divorced from clinical pathology.The essential point is that there should be a real liaison between practitioner and bacteriologist instead of the impersonal postal service which is still too prevalent.Education.-Aniost important factor in the control of infectious disease is education of the public in higher standards of personal and public hygiene.This education begins with the pre-school child,
Abstract 244: Defibrillation Efficacy Is Not Influenced by Duration of Preshock Pause
Authors: Tom F Brouwer, Robert G Walker, Fred W Chapman, Rudolph W Koster
Journal: Circulation (2012)

Background A prior small study reported a strong relationship between pre-shock pause duration (PreSP) and 1st shock defibrillation efficacy during cardiac arrest resuscitation. We examined the relationship between PreSP and defibrillation efficacy across all shocks in a large cohort of out-of-hospital cardiac arrest (OHCA) resuscitations. Methods In an observational study of prospectively collected data, we enrolled all patients with cardiac cause OHCA presenting with VT/VF during calendar year 2009 in five EMS systems. Continuous ECG and impedance recordings from all defibrillators used during resuscitation were reviewed to measure PreSP and determine outcome for all shocks. Defibrillation success was defined as removal of VF for at least 5 seconds post-shock. Results Of 902 analyzable biphasic shocks to 281 patients, 763 successfully terminated VF (85%). The median (IQR) PreSP did not differ significantly between successful and failed shocks [8 (4,17) vs 7 (5, 15) sec, p=0.34]. No significant differences were found when analyzing just first shocks [9 (4,18) vs 7 (4,15), p=0.33], just AED shocks [20 (17,23) vs 19 (15,21), p=0.31], or just manual shocks [7 (4,15) vs 7 (4,13), p=0.97]. When grouped by PreSP duration in 10-sec increments, there was no significant trend in shock efficacy with increasing pause duration (Figure, p=0.06). In a univariate regression, there was no significant relationship between first-shock PreSP duration and successful VF termination [OR = 1.15 for every 5-second increase (0.91, 1.47)]. Conclusion Defibrillation success is not associated with pre-shock pause duration.
Serum IgE concentrations in rheumatoid arthritis: lack of correlation with gold toxicity.
Authors: D M Grennan, D G Palmer
Journal: BMJ (1979)

apex rate was still 250 beats/min.Two intravenous doses of practolol had no effect.Digoxin was stopped and direct current shock, verapamil, disopyramide, and lignocaine were given to control her heart rate-all without success.When transferred to Guy's Hospital, aged 2 weeks, intracardiac electrophysiological studies showed the arrhythmia to be an ectopic upper His-bundle tachycardia with two components-a fast rate (250-300/min), which was sensitive to both lignocaine and disopyramide, and a slower rate (200-240/min), which was well tolerated but which could MexiletineDisopyramide 1-6 * 0 4 1-2 0 24 0 0 f 102- 204 c 0 °-0 - 2-0 - 0 0-8 0 O 1 6 0 o 0-6 1 2 -0 0 ~~~~~0 0 E 0.4 - 0-8 -0 o 0 (L 0 2 - 0-4 _ 00 'o 0 5 10 15 20 25 0 5 10 15 20 25 30 35Daily dose (mg/kg) Trough plasma concentrations of mexiletine and disopyramide with respect to weight-related daily doses.Open circles refer to data from case 1, closed circles to case 2.
Effects of Iloprost Inhalation on Exercise Capacity and Ventilatory Efficiency in Patients With Primary Pulmonary Hypertension
Authors: Roland Wensel, Christian F. Opitz, Ralf Ewert, Leonhard Bruch, Franz X. Kleber
Journal: Circulation (2000)

Background —The continuous infusion of prostacyclin has been shown to improve exercise capacity and survival in patients with primary pulmonary hypertension (PPH). Inhalation of iloprost, a stable analog of prostacyclin, might be an alternative therapy for PPH, selectively acting on the pulmonary vascular bed through ventilation-matched alveolar deposition of the drug. We investigated the short-term effects of iloprost inhalation on exercise capacity and gas exchange in patients with PPH. Methods and Results —In 11 patients with PPH, we performed 2 consecutive cardiopulmonary exercise tests before and after the inhalation of 17 μg of iloprost. Patients had marked pulmonary hypertension (mean pulmonary artery pressure 65 mm Hg), and inhalation resulted in a decrease in pulmonary vascular resistance (1509 versus 1175 dyne · s −1 · cm −5 , P &lt;0.05). Arterial blood gases remained unchanged (Pa o 2 69.3 versus 66.8 mm Hg; Pa co 2 29.6 versus 28.8 mm Hg). Iloprost significantly ( P &lt;0.05) improved exercise duration (379 versus 438 seconds), peak oxygen uptake (12.8 versus 14.2 mL · kg −1 · min −1 ), and V̇ e -versus-V̇ co 2 slope (58 versus 51.4). Conclusions —The present data show that iloprost inhalation exerts pulmonary vasodilatation and improves symptoms and exercise capacity in patients with PPH. The data also suggest that iloprost inhalation is a suitable treatment for PPH. Whether these effects are maintained during long-term treatment and are paralleled by improvement in prognosis remains to be determined.
Perverse financial incentives reward poor quality care, says report
Authors: M. Pownall
Journal: BMJ (2009)

New funding systems are needed to overcome the perverse financial incentives that reward the treatment of sick patients even when the ill health is caused by the system itself, concludes a major review of the evidence on quality improvement and costs.

Healthcare providers in the United Kingdom should bear more of the costs of poor quality care, which includes an absence of preventive health care, it says.

The review, by John Ovretveit, professor of health innovation and management at the Karolinska Institute in Stockholm, concludes that often the savings from improving health care are not made by the …