tbuckley/cabot-search huggingface dataset:
Toxicity of Trimethoprim-Sulphamethoxazole in Patients with Megaloblastic Haemopoiesis
Authors: I. Chanarin, J. M. England
Journal: BMJ (1972)

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.
Prostacyclin Receptor-dependent Modulation of Pulmonary Vascular Remodeling
Authors: YASUSHI HOSHIKAWA, NORBERT F. VOELKEL, TRACY L. GESELL, MARK D. MOORE, KENNETH G. MORRIS, LORI A. ALGER, SHUH NARUMIYA, MARK W. GERACI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Prostacyclin (PGI2) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction following ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI2 receptor (PGI-R) expression in the remodeled pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of 17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung histology were assessed. The PGI-R KO mice developed more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI2 and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.Key Words: knockout mice; prostacyclin receptor; pulmonary hypertension; chronic hypoxia
An aid to reducing unnecessary investigations
Authors: P. C Hayes, R. S MacWalter
Journal: BMJ (1981)

ence of one of us (SLS) in over 500 suprapubic catheterisations for postoperative bladder drainage bowel perforation has occurred on only one occasion, and was satisfactorily managed as we described.We take Miss Senapti's point that the use of a catheter with an adjustable flange may lead to urinary extravasation if the catheter is not inserted well into the bladder.Indeed, we see this as one of the advantages of the Bonanno catheter, which is our preferred instrument, since its flanges are fixed some 17j cm from the proximal side hole.
The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells
Authors: Andreas Finkensieper, Sophia Kieser, Mohamed M. Bekhite, Madeleine Richter, Joerg P. Mueller, Rolf Graebner, Hans-Reiner Figulla, Heinrich Sauer, Maria Wartenberg
Journal: Cardiovascular Research (2009)

It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated. Immunohistochemistry studies demonstrated that 5-LO+ cells first appeared at day 6 of embryoid body (EB) formation from ES cells. 5-LO+/CD68+ as well as 5-LO+/CD45+ cells were prominent at day 10 of EB differentiation. Real-time PCR and western blot analysis revealed all constituents of the 5-LO pathway. High performance liquid chromatography analyses indicated the synthesis of LTB4 and LTD4 in conformity with induction of the 5-LO pathway. Furthermore, Flk-1+/CD105+ cells displayed calcium- (Ca2+) transients in response to LTB4, whereas CD11b+ cells responded to LTD4. Treatment of EBs with LTB4 and LTD4 resulted in phosphorylation of the mitogen-activated protein kinase ERK1/2. Pharmacological inhibition of the 5-LO pathway and stable shRNA targeting of 5-LO-activating protein decreased capillary cell areas positive for PECAM-1. Our data demonstrate that the 5-LO pathway emerges early during ES cell differentiation into cells of the myeloid lineage and that LTs play an until now unrecognized role in vascular development of ES cells.
HIV is not just a transitional problem
Authors: Thomas E Novotny
Journal: BMJ (2005)

The HIV and AIDS epidemic in eastern Europe and central Asia is changing.1–2 Despite data limitations, this region shows the fastest growth in HIV in the world.3 At the end of 2004, between 920 000 and 2.1 million people in the region were living with HIV, compared with about 160 000 in 1995. Most countries in the region have low level epidemics, with less than 1% prevalence among pregnant women and less than 5% prevalence among high risk groups. The countries most affected are Ukraine, …
T-B-NK+ Severe Combined Immunodeficiency (SCID) Identified by Statewide Newborn Screening
Authors: A. Thomas, M.W. Baker, S.M. Yannone, M.J. Cowan, J.M. Puck, R.A. Gatti, A.R. Byrom, J.W. Verbsky, J.M. Routes, K.B. De Santes
Journal: Journal of Allergy and Clinical Immunology (2011)
Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria
Authors: Sayuri Yamaguchi, Tatsumi Kubota, Takahiro Yamagishi, Kiyoshi Okamoto, Tomoyuki Izumi, Masashi Takada, Shigeyuki Kanou, Mamoru Suzuki, Jun Tsuchiya, Takuji Naruse
Journal: American Journal of Hematology (1997)

Case 1: A 27-year-old woman, referred to our hospital because of relapsing fever after travel to Thailand, was given a diagnosis of vivax malaria. Clinical investigation revealed thrombocytopenia, elevated platelet-associated IgG (PAIgG), and negative antibody against Plasmodium vivax antigen. After antimalarial treatment, the levels of both the platelets and PAIgG returned to normal. Case 2: A 28-year-old Sri Lankan man was admitted to our hospital with a complaint of fever. The patient had thrombocytopenia, elevated PAIgG, and positive antibody against Plasmodium vivax antigen. He contracted malaria in Sri Lanka about 6 months prior to this admission. After treatment, the platelet count and PAIgG level returned to normal. In these two cases, high levels of PAIgG may have been involved in the development of the thrombocytopenia. In the first patient, in particular, the thrombocytopenia was thought to be induced by some immunological mechanism prior to the detection of antimaralial antibodies in serum.
Hypertension in African-Americans.
Authors: E Saunders
Journal: Circulation (1991)

A considerable disparity exists between African-Americans and US Caucasians in the incidence, severity, and management of hypertension. As a consequence, overall hypertension-related morbidity and mortality rates are at least threefold to fivefold higher in African-Americans than in Caucasians. Alarmingly high frequencies of stroke, end-stage renal disease, congestive heart failure, and left ventricular hypertrophy occur in African-Americans. To bring this crisis under control will require a renewed commitment to expanded research, improved public health measures, and more effective clinical intervention. Current hypertension control programs must be expanded and adequately funded. In addition, primary prevention of hypertension should be strongly recommended for the US population, especially African-Americans.
240 CIRCULATING CARBAMOYL PHOSPHATE SYNTHASE-1 LEVELS AS NEW PROGNOSTIC MARKER OF LIVER CELL INJURY IN CRITICALLY ILL PATIENTS
Authors: V. Fuhrmann, B. Meyer, A. Drolz, R. Saxa, T. Horvatits, J. Struck, N. Morgenthaler, G. Heinz, L. Kramer, M. Huelsmann
Journal: Journal of Hepatology (2012)
Treatment of hepatic encephalopathy with rifaximin: More to think about
Authors: Norman Gitlin
Journal: Hepatology (2010)

The recent publication of "Drug Therapy: Rifaximin" by Bajaj and Riggio1 offers interesting observations by colleagues. They voice concern that continuous rifaximin administration "could have the potential to increase resistance to rifaximin," but they cite no objective clinical data in support of their hypothesis. They also cite the two cases of Clostridium difficile in the rifaximin group reported in the registration study of rifaximin for the treatment of hepatic encephalopathy by Bass and colleagues,2 and they advise vigilance against C. difficile in patients with cirrhosis treated with rifaximin. At the US Food and Drug Administration meeting in March 2010, this matter was extensively studied and discussed. Both patients who developed C. difficile had concurrently received other antimicrobials known to cause C. difficile infection. Bajaj and Riggio's suggestion of pulse therapy with rifaximin (to reduce costs) is without precedent or merit in the realm of antimicrobial therapy. Their statement regarding rifaximin that "the current role appears to be a second-line [therapy]" is again without scientific merit. Lactulose is an effective therapy for hepatic encephalopathy; however, its use and patient compliance are severely limited and restricted by its well-recognized adverse event profile of nausea, vomiting, bloating, diarrhea, and incontinence. Rifaximin is very well tolerated, and it not only improves the duration of remission of hepatic encephalopathy but also lessens the need for repeated hospitalization.2 Both factors require consideration when one is calculating the overall cost of the two agents, their beneficial effects, and patient preference, compliance, and quality of life. Norman Gitlin M.D.*, * Atlanta Gastroenterology Associates, Atlanta, GA.
Cerebrospinal Fluid Protein Concentration in Hepatic Coma
Authors: Dan Dillon
Journal: JAMA (1972)

<h3>To the Editor.—</h3> We have recently cared for a patient with alcohol-induced cirrhosis of the liver and hepatic coma who manifested an elevated cerebrospinal fluid (CSF) protein concentration as the sole other abnormal finding. Because of this laboratory finding, further studies were carried out and the patient was eventually found to have cryptococcal meningitis in addition to hepatic coma. With appropriate therapy, the patient improved. This case directed our attention to CSF protein concentration in hepatic coma. There are very few published reports on CSF protein concentration in hepatic coma and these are conflicting.<sup>1,2</sup>The standard current textbooks in internal medicine, neurology, and gastroenterology do not address themselves to this issue. Two exceptions are the discussions by Sherlock and Fishman wherein it is mentioned that CSF protein concentration in hepatic coma may be increased.<sup>3-4</sup>The frequency and magnitude of the elevated protein concentration, however, are not mentioned. In
EBV negative Richter's syndrome from a coexistent clone after salvage treatment with alemtuzumab in a CLL patient
Authors: Ann Janssens, Mario Berth, Pascale De Paepe, Bruno Verhasselt, Nadine Van Roy, Lucien Noens, Jan Philippé, Fritz Offner
Journal: American Journal of Hematology (2006)

Abstract Transformation of B cell chronic lymphocytic leukemia (B‐CLL) to large cell lymphoma or Hodgkin's disease is known as a Richter's syndrome (RS). According to the literature, 1–10% of B‐CLL patients develop this high‐grade lymphoid malignancy. The relationship between the immunosuppressive effect of nucleoside analogues (NA) and monoclonal antibodies and the development of large cell transformation still remains a controversial issue. We describe a CLL patient who developed a large B cell lymphoma 94 months after diagnosis and 3 months after the start of alemtuzumab. The CLL immunophenotype was retained by the transforming cells although a different light chain was expressed. Molecular analysis of the immunoglobulin heavy chain confirmed that the CLL and the RS had a different clonal origin. Subsequent molecular analyses of stored samples showed that the clone with transforming capacity already appeared two years before the clinical appearance of the RS. We hypothesize that alemtuzumab promoted the uncontrolled growth of the latest clone by eradicating the initial B‐CLL clone efficiently, and by inducing a strong T cell depletion with consequent impairment of the immunosurveillance. We also ruled out that the RS was EBV driven. In conclusion, we report a case of EBV negative RS after alemtuzumab as salvage therapy. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Longitudinal Assessment of Quality of Life in Patients With Type 2 Diabetes and Self-Reported Erectile Dysfunction
Authors: Giorgia De Berardis, Fabio Pellegrini, Monica Franciosi, Maurizio Belfiglio, Barbara Di Nardo, Sheldon Greenfield, Sherrie H. Kaplan, Maria C.E. Rossi, Michele Sacco, Gianni Tognoni, Miriam Valentini, Antonio Nicolucci
Journal: Diabetes Care (2005)

OBJECTIVE—In the context of the QuED (Quality of Care and Outcomes in Type 2 Diabetes) project, we evaluated the longitudinal changes over 3 years in quality of life (QoL) in patients with type 2 diabetes according to the presence or the development of erectile dysfunction (ED). RESEARCH DESIGN AND METHODS—Patients were requested to fill in a questionnaire investigating the presence of ED and QoL (SF-36 Health Survey, depression symptoms [Center for Epidemiologic Studies–Depression], and quality of sexual life) every 6 months for 3 years. The analyses were based on multilevel models, adjusted for patient clinical and sociodemographic characteristics. RESULTS—The study involved 1,456 patients, of whom 34% reported frequent erectile problems at baseline; 192 developed ED during the follow-up. No changes in QoL measures were detected in patients without ED; in those with ED at baseline, a worsening in all SF-36 scales was observed, reaching statistical significance for physical functioning (P = 0.03). Among patients who developed ED during the study, a deterioration in all SF-36 dimensions and a worsening in depressive symptoms preceded the development of ED. The onset of ED was associated with a further marked worsening in physical functioning (P = 0.0008), general health perception (P = 0.02), and social functioning (P = 0.04) on SF-36 subscales, as well as in the summary physical and mental components scores (P = 0.04 and P = 0.07, respectively). The development of ED was also associated with a highly significant increase in depressive symptoms (P = 0.001) and a marked decrease in quality of sexual life (P &amp;lt; 0.0001). CONCLUSIONS—This longitudinal study documents for the first time the impact of ED onset on several aspects of QoL in patients with type 2 diabetes. The study also shows that QoL tended to further decrease during 3 years in patients with ED at baseline but not in those without this condition.
Influence of Digitalis on Time of Onset and Duration of Labour in Women with Cardiac Disease
Authors: J. B. Weaver, J. F. Pearson
Journal: BMJ (1973)

A comparison was made of the time of onset and duration of labour in 22 women taking digitalis and in 64 women who were not. Spontaneous labour occurred more than one week earlier and lasted about half as long in the patients taking digitalis. The likely explanation for this difference is that digitalis has a direct action on the myometrium.
Rates of medication errors among depressed and burnt out residents: prospective cohort study
Authors: Amy M Fahrenkopf, Theodore C Sectish, Laura K Barger, Paul J Sharek, Daniel Lewin, Vincent W Chiang, Sarah Edwards, Bernhard L Wiedermann, Christopher P Landrigan
Journal: BMJ (2008)

<b>Objective</b> To determine the prevalence of depression and burnout among residents in paediatrics and to establish if a relation exists between these disorders and medication errors. <b>Design</b> Prospective cohort study. <b>Setting</b> Three urban freestanding children’s hospitals in the United States. <b>Participants</b> 123 residents in three paediatric residency programmes. <b>Main outcome measures</b> Prevalence of depression using the Harvard national depression screening day scale, burnout using the Maslach burnout inventory, and rate of medication errors per resident month. <b>Results</b> 24 (20%) of the participating residents met the criteria for depression and 92 (74%) met the criteria for burnout. Active surveillance yielded 45 errors made by participants. Depressed residents made 6.2 times as many medication errors per resident month as residents who were not depressed: 1.55 (95% confidence interval 0.57 to 4.22) compared with 0.25 (0.14 to 0.46, P&lt;0.001). Burnt out residents and non-burnt out residents made similar rates of errors per resident month: 0.45 (0.20 to 0.98) compared with 0.53 (0.21 to 1.33, P=0.2). <b>Conclusions</b> Depression and burnout are major problems among residents in paediatrics. Depressed residents made significantly more medical errors than their non-depressed peers; however, burnout did not seem to correlate with an increased rate of medical errors.
Jean Mary Scott (nee Neville)
Authors: J. Cook, J. Short, D. A. Cruikshank
Journal: BMJ (2011)

Jane Cook and Jane Short write:

Dr Scott, who became a considerable force in medical politics as regards the status of women doctors, died suddenly at her home in Pitlochry, Perthshire, on 5 November, 2010.

She was born on 18 September 1921 in Airdrie, Lanarkshire, and, following school in school in Coatbridge, she attended Glasgow University graduating MB ChB in 1944 followed by an MD with commendation in 1948. Her thesis was on anaemia in pregnancy, and in 1949 her first paper on this topic was published in the British Medical Journal . This led to her becoming an internationally known expert on the subject. She established the first antenatal blood clinic in the west of Scotland and showed clearly that anaemia was the most common and serious complication of pregnancy. Dr Scott worked as a clinical pathologist in many Glasgow hospitals, her last appointment being at the Glasgow Royal Maternity Hospital and Wolfson Medical School at Strathclyde University.

After her formal retirement she continued to serve on committees furthering good causes of which she approved—the National Trust for Scotland, the Pitlochry Civic Trust, the Pitlochry Conservation Society, the WRVS, and the local church.

She continued cycling till the year prior to her death, when she re-cycled her bicycle to a child in Malawi.

Her husband predeceased her in 1995, but she continued to care for her garden in Pitlochry with its magnificent collection of rhododendrons.

Dr Scott is survived by her daughter, Marion, and son in law, Geoff, in Canada.

David A Cruikshank writes in his eulogy for Dr Scott:

An esteemed and highly respected lady.

Consultant haematologist and pathologist of international renown in her working life and for many years after her retiral in 1981.

Known as Dr Scott to so many who new her—her doctorate a fitting …
A Contribution to the Surgical Treatment of Diseases of the Appendix Vermiformis
Authors: W. H. Battle
Journal: BMJ (1897)

MBILDCAL 965 two well-marked attacks of appendicitis, especially if the physical signs-more particularly a swelling in the situation of the appendix-persist in the quiescent period after the subsidence of the attacks.In two of the three patients operated upon after a second attack (Cases vi, vii) small collections of pus were found in the immediate neighbourhood of the appendix, while in the third patient (Case iii) the appendix was distended with fluid and upon the point of rupture.In another patient, operated upon after a third attack (Case iv), a hard faecal concretion was found in the appendix, probably the cause of the preceding attacks.When an appendix is constricted or occluded, and especially when it is distended with fluid or contains a faecal concretion, tllere is always a risk of ulcera- tion and perforation taking place, followed by escape of its contents and suppuration around it.Owing, however, to the fact that the appendix is under these conditions generally surrounded by adhesions, which act as a protective barrier, shutting off the general peritoneal cavity, this complication, as already mentioned, is usually followed by a local or encysted abscess, which may, however, sometimes form with acute symptoms, as in the following case.CASE IX.Recurrent Attacks for Several Years: Szdden Formation of an Acute Abscess: Incision and Drainage: Recovery.-Amale, aged 26 years, seen in consultation with Dr. John Watson on March 14th, i896.and operated upon the same day.For more than three years he had suffered at irregular intervals from frequent attacks of a mild type.Tlhree weeks previously more acute symptoms suddenly developed, followed by the formation of an abscess, which became most prominent on the outer aspect of the caecum.it was opened and about a pint of pus with a very offensive fecal odour was evacuated.The abscess cavity was drained, no attempt being made to remove the appendix, and the patient made a satisfactory recovery.
GR106642X: a new, non-ozone depleting propellant for inhalers
Authors: S. C O Taggart, A. Custovic, D. H Richards, A. Woodcock
Journal: BMJ (1995)

Metered dose inhalers are the most popular choice of drug delivery system for treating asthma and chronic airflow limitation. Unfortunately, they contain chlorofluorocarbon propellants, which contribute to the depletion of stratospheric ozone.1 The Montreal Protocol of 1987 has therefore called for a gradual phasing out of manufacture of chlorofluorocarbons in all developed countries by 1996. Inhalers containing chlorofluorocarbons have been given a temporary exemption, but there remains considerable environmental pressure for their early withdrawal.

GR106642X (1, 1, 1, 2-tetrafluoroethane) is a new propellant which does not deplete ozone. It has been used alone, with no other excipients, to reformulate salbutamol. We investigated the safety and efficacy of the new non-ozone depleting formulation for salbutamol in a randomised, double blind, placebo controlled, crossover comparison with the traditional salbutamol inhaler containing chlorofluorocarbons 11 and 12 (Ventolin, Allen …