tbuckley/cabot-search huggingface dataset:
Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels.
Authors: J L Data, B A Molony, M M Meinzinger, R R Gorman
Journal: Circulation (1981)

Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were tolerated at rates up to 10.0 ng/kg/min; higher rates produced headaches, anxiety, nausea and vomiting. Six-hour and 24-hour infusions were tolerated at rates up to only 4.0 ng/kg/min. Twenty-four hour infusions at 4 ng/kg/min produced a consistent 4-7 microM shift to the right in the platelet ADP dose-response curve; this platelet inhibitory activity did not diminish during the infusion. Prostacyclin sodium infusion elevated intracellular cyclic AMP levels, the increases corresponding to the onset of measurable inhibition of ADP-induced aggregation, although the magnitude of the increase did not necessarily reflect the degree of inhibition. Increased template bleeding times were seen with a greater than 10-microM shift in the ADP dose-response curve. We conclude that although prostacyclin sodium has a narrow safety margin, the drug does produce platelet inhibition at infusion rates generally tolerated by healthy volunteers.
Good Drug, Bad Luck: Business, Regulatory Issues Can Create Obstacles for Drug Development
Authors: B. Goldman
Journal: JNCI Journal of the National Cancer Institute (2004)

Anybody involved with cancer knows that bad things happen to good people.Sometimes bad things happen to good cancer drugs, too, for reasons ranging from regulatory red tape to intellectual property constraints.The stories of two drugs-one an oral chemotherapy, the other a bone-seeking radiopharmaceutical-show how regulatory or licensing barriers can block a promising compound's path.
Selenium and Vitamin E Supplementation for Cancer Prevention
Authors: Rachel Hurst, Susan Fairweather-Tait
Journal: JAMA (2009)

To the Editor: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) by Dr Lippman and colleagues reported that selenium or vitamin E alone or in combination did not prevent prostate cancer. The negative results of this trial confirm the outcomes in the Nutritional Prevention of Cancer (NPC) Trial for those participants with the highest baseline plasma selenium concentration prior to supplementation with selenized yeast. The conclusion from both NPC and SELECT should be that daily selenium supplementation will not benefit all persons. Cancer risk reduction with selenium should be expected only in men with low or suboptimal levels prior to supplementation. A U-shaped dose-response relationship between selenium intake and cancer risk, as suggested by studies in dogs, is consistent with the results of SELECT and NPC. At baseline, the average participant in SELECT had selenium status within the trough of the U-shaped curve, ie, not low or suboptimal. After supplementation with 200 μg per day of selenium as selenomethionine, the average SELECT participant achieved selenium levels that far exceeded the high postsupplementation values of men in NPC in the highest baseline-selenium tertile. Those NPC participants experienced no prostate-cancer risk reduction and an almost 3-fold increased incidence of diabetes. In SELECT, there was no reduction in prostate-cancer risk and a statistically nonsignificant increased diabetes incidence. We therefore consider the results of SELECT and NPC to be consistent, not contradictory. We believe that it is time to move beyond the belief that any particular agent administered at the same dose to all participants will benefit the overall population and instead attempt to individualize cancer prevention. Subsets of individuals should be identified who are more likely to benefit from supplementation, such as persons with low selenium concentrations or perhaps those with the selenoprotein-P genotype that is associated with prostatecancer risk. This stance is distinct from claiming knowledge of which types of cancer will or will not be prevented by selenium.
Galantamine may be effective in treating autistic disorder
Authors: H. Niederhofer
Journal: BMJ (2002)

EDITOR—Wilcock et al report galantamine to be an effective and well tolerated drug in Alzheimer's disease.1 The mechanisms of autistic disorders are not completely understood. At least one kind of autism (Heller's dementia) is clinically quite similar to Alzheimer's disease.

No specific drugs seem to improve autism significantly. Desipramine, dextroamphetamine, clonidine, neuroleptics, and methylphenidate are reported to be only slightly effective but also to have possible severe adverse …
Some contributions to regio and stereo control: From cincholoipon and cantharidin to the present
Authors: Gilbert Stork
Journal: Medicinal Research Reviews (1999)

A condensed review of some of the major original contributions of the author's research group to organic synthesis during more than half a century. The emphasis is on methodology, especially as it involves the control of regio- and stereochemistry. The application of these methods in the total synthesis of specific natural products in the author's laboratory is not discussed in extenso, but only by focusing on certain key steps which illustrate the application of the methods mentioned here. Methods discussed in this fashion are: cationic polyene cyclizations; the enamine alkylation and acylation of ketones and aldehydes; the metalloenamine alkylation; the regiospecific formation and trapping of enolates, via electron addition or via conjugate addition of organometallic reagents to enones; regiospecific enolate formation-trapping from saturated ketones and from β-alkoxy enones; the epoxynitrile and the allylic epoxynitrile cyclizations; the cyclization of olefinic diazoketones; the cyclization of alkynyl ketones; protected cyanohydrins as acylcarbanion equivalents; the vinyl radical cyclization; the control of regio- and stereochemistry via radical cyclization to temporary rings. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 5, 370–387, 1999.
Sequential treatment of biliary atresia with kasai portoenterostomy and liver transplantation: A review†
Authors: Jean-Bernard Otte, Jean De Ville De Goyet, Raymond Reding, Victoria Hausleithner, Etienne Sokal, Christophe Chardot, Benoit Debande
Journal: Hepatology (1994)

Biliary atresia is the most frequent cause of chronic cholestasis in infants. When left untreated, this condition leads to death from liver insufficiency within the first 2 yr of life. The modern therapeutic approach consists of a sequential strategy with Kasai portoenterostomy as a first step and, in case of failure, liver transplantation. After portoenterostomy, no more than 20% to 30% of patients will live jaundice-free into adulthood. Illness in another third will be palliated, and these patients have extended survival, delaying liver transplantation to later childhood (2 to 15 yr). The remaining 30% to 40% will not benefit from the Kasai operation and will die of liver failure in infancy. The annual need of liver transplantation for biliary atresia is one case per million people. This indication represents 35% to 67% of the reported series of pediatric liver transplantation and between 5% and 10% of the indications for liver transplantation, all ages included. Approximately four of five children transplanted for biliary atresia will become long-term survivors with good physical and mental development; recurrence of the disease after transplantation has not been observed. Because most candidates are young children (&lt;3 yr) of small size (&gt;10 kg), there is a shortage of size-matched donors (which has been alleviated by the use of innovative techniques such as reduced and split livers). The resulting redistribution of the adult donor liver pool is ethically justified by the equal quality of the results after transplantation of a full-size or partial graft. (Hepatology 1994;20:41S-48S.)
Effect of corticosteroid therapy on levels of antibody to hepatitis B core antigen in patients with chronic type B hepatitis
Authors: Maria H. Sjogren, Jay H. Hoofnagle, Jeanne G. Waggoner
Journal: Hepatology (1987)

Serum levels of antibody to hepatitis B core antigen and IgM antibody to hepatitis B core antigen were tested in 15 patients who participated in a randomized, placebo-controlled trial of a 28-day course of prednisolone therapy. During treatment, serum levels of antibody to hepatitis B core antigen and IgM antibody to hepatitis B core antigen decreased in all 10 treated patients, but in none of five controls (p < 0.05). Also during therapy, ALT activity decreased by an average of 50% and serum IgG levels by 30% (both p <: 0.05). Serum levels of hepatitis B virus DNA and DNA polymerase activity did not change significantly. Four to 10 weeks after discontinuation of prednisolone, a rebound of serum ALT and IgM antibody to hepatitis B core antigen levels occurred, which usually resolved within the subsequent months of follow-up evaluation. In three patients, however, there was a prolonged exacerbation of the disease following prednisolone withdrawal; in these three, levels of IgM antibody to hepatitis B core antigen and ALT remained elevated above pretreatment values. The close correlation between changes in serum ALT activity and IgM antibody to hepatitis B core antigen levels suggests that corticosteroids can modulate disease activity in chronic type B hepatitis by suppression of the host-immune response to hepatitis B virus antigens.
Sir James Y. Simpson
Authors: Phoebe Peck
Journal: New England Journal of Medicine (1961)

TO many, Simpson's name is associated with the discovery of chloroform in obstetrics and perhaps with the long forceps. His achievements in other fields, particularly archaeology, are not so well known.Sir James Young Simpson (Fig. 1) was born June 7, 1811, in Bathgate, Linlithgowshire, the seventh son of the village baker. He received his medical degree in 1832 from the University of Edinburgh. Seven years later, when twenty-eight, he was elected by the Town Council to be professor of midwifery, the election being won by one vote. This proved to be a popular decision with the students, and, for . . .
MURDER AS A REACTION TO PARANOID DELUSIONS IN INVOLUTIONAL PSYCHOSIS AND ITS PREVENTION
Authors: JOHN LANZKRON
Journal: American Journal of Psychiatry (1961)

Eight short case histories were presented of patients admitted to Matteawan State Hospital for the Criminal Insane charged or indicted with murder, first degree, occurring as a reaction to paranoid delusions of an involutional psychosis. In all of these cases, forebodings of the malignant nature of patient's mental illness were present. This would indicate that these patients harbored potential homicidal tendencies for a prolonged period of time. A patient in the involutional period with potential homicidal tendencies as a reaction to paranoid delusions, should be hospitalized as a preventive measure as early as possible, the same as is done with potential suicidal patients.
New Primary Neoplasms of the Central Nervous System in Survivors of Childhood Cancer: a Report From the Childhood Cancer Survivor Study
Authors: Joseph P. Neglia, Leslie L. Robison, Marilyn Stovall, Yan Liu, Roger J. Packer, Sue Hammond, Yutaka Yasui, Catherine E. Kasper, Ann C. Mertens, Sarah S. Donaldson, Anna T. Meadows, Peter D. Inskip
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose–response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. Methods: Subsequent primary neoplasms of the CNS occurring within a cohort of 14 361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site–specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data. Results: Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10 000 person-years. Conclusions: Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.
Patient outcomes at both ends of the stethoscope
Authors: C. McDermott
Journal: BMJ (2014)

Politics influences health policy and practice.With the European and local council election results just out, questions of priority setting may well be at the front of our minds.Within that context, a longitudinal study in this week's journal seeks to assess whether targeted spending in deprived areas has reduced the health outcomes gap.The study by Barr and colleagues (doi:10.1136/bmj.g3231)looks at the impact of a government initiative that saw the NHS resource allocation formula adjusted to achieve this objective across the 324 local authorities in England.
Jefferson Medical College: Legend and Lore
Authors: Howard Spiro
Journal: JAMA (1997)

An extraordinarily engaging book,<i>Jefferson Medical College: Legend and Lore</i>is a labor of love to "record an institution's tradition and history" as its President, Paul C. Brucker, writes in the foreword. I was doubtful about the tome, the third in the trilogy of Jefferson's history, but it is beguiling to dip into its 15 chapters. They cover everything from the founding of the school, medical student life in the 19th century, alumni who founded other medical colleges, unusual Jefferson alumni, alumni who attended US presidents, eminent professors, and much more. I knew that the DaCostas were graduates of "Jeff," that Chevalier Jackson and Hobart Reimann had graced its corridors, but that Dercum of "Dercum's Disease" and John Gibbon of the heart-lung machine had worked there was news. There are chapters on early black alumni (the first identifiable black graduate, Algernon Jackson, graduated in 1901) and on early Jewish graduates
Sun protective behaviour of vacationers spending holidays in the tropics and subtropics
Authors: D. Reinau, C. Achermann, N. Arnet, C.R. Meier, C. Hatz, C. Surber
Journal: British Journal of Dermatology (2014)

The development of malignant melanoma has been associated with intense episodic sun exposure, as it typically occurs during holidays in high ultraviolet (UV)-index countries.To investigate sun protective behaviour and sunburn experience of vacationers spending holidays in the tropics or subtropics.Using standardized face-to-face interviews, we conducted cross-sectional surveys among air passengers waiting in the departure or the baggage claim area at the Airport Basel-Mulhouse (Switzerland/France), and among vacationers waiting for pretravel health advice at a travel clinic in Basel (Switzerland).We completed 533, 324 and 308 interviews with departing air passengers, returning air passengers and vacationers at the travel clinic, respectively. The interviews revealed widespread misconceptions about how to prepare the skin for the sun before holidays (e.g. pretanning in the solarium). At the holiday destination, almost all respondents used sunscreen, whereas wearing protective clothing and seeking shade were less practised. Among the returning air passengers, 44% had got sunburnt during their holiday stay.The sunburn rate among returning vacationers was alarmingly high. Skin cancer prevention campaigns and pretravel health advice should tackle misconceptions regarding the preparation of the skin for the sun, and emphasize the significance of covering up and seeking shade.
Vitamin K policies and midwifery practice: questionnaire survey
Authors: Pat Ansell, Eve Roman, Nicola T Fear, Mary J Renfrew
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To investigate policies on neonatal vitamin K and their implementation. <b>Design:</b> Two phase postal survey. <b>Setting:</b> United Kingdom. <b>Participants:</b> A 10% random sample of midwives registered with the United Kingdom Central Council for nursing, midwifery, and health visiting. Of 3191 midwives in the sample, 2515 (79%) responded to phase one and 2294 (72%) completed questionnaires on their current jobs (November 1998 to May 1999). In phase two, 853 (62%) of 1383 eligible midwives gave details on 2179 of their earliest jobs (start dates before 1990). <b>Results:</b> All the midwives in clinical practice at the time of the survey (2271, 99%) reported that they were working in areas with official policies on neonatal vitamin K. Seven distinct policies were described: intramuscular vitamin K for all babies (1159, 51.0%); intramuscular vitamin K for babies at “high risk,” oral for others (470, 20.7%); oral vitamin K for all babies (323, 14.2%); parental choice for all (124, 5.5%); parental choice for all except babies at high risk, (119, 5.2%); intramuscular vitamin K for babies at high risk only (33, 1.5%); oral vitamin K for babies at high risk only (17, 0.7%); and a disparate group of policies including intravenous vitamin K for some babies (26, 1.1%). Previous policies were (and some may still be) open to individual interpretation and were not always followed. <b>Conclusions:</b> Hospital policy is not necessarily a good guide to individual practice. The primary purpose of clinical records is to document patient care, and recording practices reflect this. There is considerable variation in vitamin K policies and midwifery practice in the United Kingdom, and there is no clear consensus on which babies should receive vitamin K intramuscularly. <h3>What is already known on this topic</h3> Neonatal administration of vitamin K by the intramuscular route is effective in the prevention of haemorrhagic disease in newborn babies but has been suggested as a possible risk factor for leukaemia in children A written record confirming that vitamin K has (or has not) been given is often not found, and some research groups have attempted to impute a child9s vitamin K status from hospital policy Nothing is known about how midwives interpret and implement vitamin K policies <h3>What this study adds</h3> Earlier hospital policies were open to individual interpretation and they were not always followed There is considerable variation in current vitamin K policies and midwifery practice in the United Kingdom and no clear consensus on which babies should receive vitamin K intramuscularly
F-18 FDG Whole-Body PET for the Assessment of Disease Activity in Patients With Rheumatoid Arthritis
Authors: Gerhard W. Goerres, Adrian Forster, Daniel Uebelhart, Burkhardt Seifert, Valerie Treyer, Beat Michel, Gustav K. von Schulthess, Achim H. Kaim
Journal: Clinical Nuclear Medicine (2006)

PURPOSE OF REPORT: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate if a simple scoring system based on visual assessment of FDG joint uptake correlates with the clinical assessment of patients with RA undergoing antiinflammatory treatment.Seven patients with active RA underwent whole-body FDG PET and clinical assessment before and after treatment with the antitumor necrosis factor alpha antibody (infliximab). A PET total joint score, ie, the sum of all scores based on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a total joint score based on the clinical disease activity in the same joints using a Spearman rank correlation.The PET based total joint score was similarly high before onset as was the clinical total joint score. The decrease of FDG joint uptake in the follow-up PET scans correlated significantly with the clinical assessment. Additionally, synovial FDG uptake was found in extraarticular sites such as tendon sheaths and bursae.Visual assessment of FDG uptake shows a significant correlation with clinical evaluation of disease activity in patients with RA undergoing antiinflammatory treatment.
Positions During Labour
Authors: D. P. C. Chan
Journal: BMJ (1963)

proved as satisfactory as 70 specimens obtained by the more elaborate tube method described by Leather and Hutchings (1960).Furthermore, failure to obtain a specimen using the tube technique occurred in over 50% of the patients in whom it was attempted.A technique for performing bacterial counts on surface plates using a fused platinum loop is described, and it compared with the standard pour-plate technique.Counts obtained by both methods agree in 89% of specimens examined, and all but one of the discrepancies were of a minor character.Thus the loop technique provides a simplified method of quantitative urine culture suitable for routine laboratories.Bacterial counts have been compared with the independent routine laboratory reports on 100 consecu- tive urine specimens.The results agree in 90% of samples.In no case was significant bacteriuria over- looked by the routine laboratory.However, the use of bacterial counts halved the number of equivocal results.These findings cast doubt on the necessity for quantitative urine culture in routine practice.
Plasma carboxypeptidases as regulators of the plasminogen system.
Authors: A Redlitz, A K Tan, D L Eaton, E F Plow
Journal: Journal of Clinical Investigation (1995)

Carboxy-terminal lysine residues on the surface of cells and fibrin bind plasminogen and control its activation.Since plasma contains basic carboxypeptidases, which remove carboxy-terminal lysines from protein substrates, we inves- tigated if these enzymes are involved in the regulation of plasminogen binding sites.Plasma reduced plasminogen binding to cells, and this effect could be ascribed to the activity of the plasma carboxypeptidases.Purified carboxypeptidase N, which is constitutively active, and plasma car- boxypeptidase B, which circulates as a zymogen, were both capable of significantly reducing plasminogen binding to cells.Dose titration experiments verified that plasma con- centrations of either carboxypeptidase were sufficient to maximally affect plasminogen binding to cells.Further- more, plasma carboxypeptidase B, but not carboxypeptidase N, reduced the rate of whole blood clot lysis induced by tissue-type plasminogen activator.These findings establish that plasma carboxypeptidases can modulate plasminogen binding to cells and control the rate of fibrinolysis.These functions delineate a novel role for the plasma carboxypeptidases in the regulation of the plasminogen system.(J.Clin.Invest.