tbuckley/cabot-search huggingface dataset:
A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis
Authors: J. BERTH-JONES, A.C. CHU, W.A.H. DODD, M. GANPULE, W.A.D. GRIFFITHS, R.P. HAYDEY, M.R. KLABER, S.J. MURRAY, S. ROGERS, H.J. JURGENSEN
Journal: British Journal of Dermatology (1992)

Short‐contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel‐group comparison was performed. Four hundred and seventy‐eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 μg/g) twice daily. The other used a single application for 30 min each day of Dithrocream© in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five‐point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P<0.001), and from 9.4 to 3.4 on calcipotriol (P<0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P<0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5–2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol. The mean serum calcium showed no increase in either group. Calcipotriol was more effective and better accepted than short‐contact dithranol. Both treatments appeared free from serious adverse effects.
Metoclopramide and Edema
Authors: BARNETT ZUMOFF
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 April 1983Metoclopramide and EdemaBARNETT ZUMOFF, M.D.BARNETT ZUMOFF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-4-557_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The review (1) of the pharmacology of metoclopramide touched so briefly on its effects on plasma aldosterone levels (2) to imply that these effects are of no clinical significance. A recent patient of mine showed that this may not always be the case.An 82-year-old man who had had a subendocardial infarct 8 weeks earlier and then developed mild and fairly stable congestive heart failure was treated with digoxin and mild salt restriction. One month after the infarct, the patient complained of upper abdominal distention, nausea, and anorexia, and was given a 2-week course of oral metoclopramide,...References1. ALBIBI R and MCCALLUM R. Metoclopramide: pharmacology and clinical application. Ann Intern Med. 1983;98:86-95. LinkGoogle Scholar2. NORBIATO G, BEVILACQUA M, RAGGI U, MICOSSI P, and MORONI C. Metoclopramide increases plasma aldosterone concentrations in man. J Clin Endocrinol Metab. 1977;45:1313-6. CrossrefMedlineGoogle Scholar3. AUGUST J, NELSON D, and THORN G. Response of normal subjects to large amounts of aldosterone. J Clin Invest. 1958;37:1549-55. CrossrefMedlineGoogle Scholar4. NELSON D and AUGUST J. Abnormal response of oedematous patients to aldosterone or deoxycortone. Lancet. 1959;2:883-5. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: BARNETT ZUMOFF, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1983Volume 98, Issue 4Page: 557-557KeywordsAldosteroneBlood plasmaClinical pharmacologyEdemaHeart failureNauseaPharmacologySalts ePublished: 1 December 2008 Issue Published: 1 April 1983 PDF downloadLoading ...
Effects of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated neonatal and adult rabbit hearts
Authors: T Murashita, D J Hearse, M Avkiran
Journal: Cardiovascular Research (1991)

Journal Article Effects of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated neonatal and adult rabbit hearts Get access T Murashita, T Murashita T Murashita, D J Hearse, M Avkiran, Cardiovascular Research, The Rayne Institute, St Thomas's Hospital, London SE1 7EH, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar D J Hearse, D J Hearse T Murashita, D J Hearse, M Avkiran, Cardiovascular Research, The Rayne Institute, St Thomas's Hospital, London SE1 7EH, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar M Avkiran M Avkiran T Murashita, D J Hearse, M Avkiran, Cardiovascular Research, The Rayne Institute, St Thomas's Hospital, London SE1 7EH, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 6, June 1991, Pages 496–502, https://doi.org/10.1093/cvr/25.6.496 Published: 01 June 1991 Article history Received: 17 September 1990 Accepted: 26 February 1991 Published: 01 June 1991
Designing Clinical Research: An Epidemiologic Approach
Authors: Don Riesenberg
Journal: JAMA (1989)

"Why this sample size?" "But those aren't parametric data." "That's not an appropriate control group!" So it goes when editors meet to decide which studies to publish and which not. There is lots of wondering aloud, mixed with colorful editorial epithets, about why investigators conceived, carried out, and reported their project this way rather than that. These deliberations turn on two points: Is the work valid and will the reader gain from having seen it? Such questions imply, rightly so I think, that the reporting of research is a collaborative effort between those who do it and those who read it. Only in the last decade has this been fully realized by the clinical epidemiologists who are in a position to do something about it. Many books, great and small (not a few of which have been reviewed in these pages), have appeared in an attempt to explain how valid
Serotonin and depression
Authors: D. Healy
Journal: BMJ (2015)

The marketing of a myth

The serotonin reuptake inhibiting (SSRI) group of drugs came on stream in the late 1980s, nearly two decades after first being mooted. The delay centred on finding an indication. They did not have hoped for lucrative antihypertensive or antiobesity profiles. A 1960s idea that serotonin concentrations might be lowered in depression1 had been rejected,2 and in clinical trials the SSRIs lost out to the older tricyclic antidepressants as a treatment for severe depression (melancholia).3 4 5

When concerns emerged about tranquilliser dependence in the early 1980s, an attempt was made to supplant benzodiazepines with a serotonergic drug, buspirone, marketed as a non-dependence producing anxiolytic. This flopped.6 The lessons seemed to be that patients expected tranquillisers to have an immediate effect and doctors expected them to produce dependence. It was not possible to detoxify the tranquilliser brand.

Instead, drug companies marketed SSRIs for depression, even though they were weaker than older tricyclic antidepressants, and sold the idea that depression was the deeper illness behind the superficial manifestations of anxiety. The approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied …
Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens.
Authors: Helen Tinwell, John Ashby
Journal: Environmental Health Perspectives (2004)

We have evaluated whether mixtures of estrogens, present in the mix at doses that are individually inactive in the immature rat uterotrophic assay, can give a uterotrophic response. Seven chemicals were evaluated: nonylphenol, bisphenol A (BPA), methoxychlor, genistein (GEN), estradiol, diethylstilbestrol, and ethinyl estradiol. Dose responses in the uterotrophic assay were constructed for each chemical. The first series of experiments involved evaluating binary mixtures of BPA and GEN at dose levels that gave moderate uterotrophic responses when tested individually. The mixtures generally showed an intermediate or reduced uterotrophic effect compared with when the components of the mixture were tested alone at the dose used in the mixture. The next series of experiments used a multicomponent (complex) mixture of all seven chemicals evaluated at doses that gave either weakly positive or inactive uterotrophic responses when tested individually in the assay. Doses that were nominally equi-uterotrophic ranged over approximately six orders of magnitude for the seven chemicals. Doses of agents that gave a weak uterotrophic response when tested individually gave a marginally enhanced positive response in the assay when tested combined as a mixture. Doses of agents that gave a negative uterotrophic response when tested individually gave a positive response when tested as a mixture. These data indicate that a variety of different estrogen receptor (ER) agonists, present individually at subeffective doses, can act simultaneously to evoke an ER-regulated response. However, translating these findings into the process of environmental hazard assessment will be difficult. The simple addition of the observed, or predicted, activities for the components of a mixture is confirmed here to be inappropriate and to overestimate the actual effect induced by the mixture. Equally, isobole analysis is only suitable for two- or three-component mixtures, and concentration addition requires access to dose-response data and EC50 values (concentration giving 50% of the maximum response) for the individual components of the mixture--requirements that will rarely be fulfilled for complex environmental samples. Given these uncertainties, we conclude that it may be most expedient to select and bioassay whole environmental mixtures of potential concern.
Cannabis based drug is licensed for spasticity in patients with MS
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The first drug derived from the cannabis plant to be granted a licence by UK authorities has been made available for relief of spasticity in patients with multiple sclerosis.

Sativex oromucosal spray, from Bayer Schering Pharma UK, is indicated as an add-on treatment for patients with moderate to severe spasticity from multiple sclerosis who do not respond adequately to other antispasticity drugs and who show a clinically significant response during an initial trial of the treatment. It contains two cannabinoids in equal quantities: cannabidiol and delta-9-tetrahydrocannabinol.

Spasticity is a common symptom in people with multiple …
TGF-beta promotes proliferation of cultured SMC via both PDGF-AA-dependent and PDGF-AA-independent mechanisms.
Authors: G A Stouffer, G K Owens
Journal: Journal of Clinical Investigation (1994)

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in mediating smooth muscle cell (SMC) growth after vascular injury. Studies examining TGF-beta-induced growth of cultured SMC have identified only modest mitogenic effects which are largely dependent on autocrine production of platelet-derived growth factor-AA (PDGF-AA). Recent studies have suggested, however, that TGF-beta also may have delayed growth effects independent of PDGF-AA. The aims of the present studies were to examine the effects of TGF-beta on chronic growth responses of cultured SMC. Results demonstrated that TGF-beta elicited a delayed growth response (24 fold increase in 3H-TdR incorp. from 48-72 h) and enhanced SMC production of PDGF-AA (eightfold increase at 24 h). Neutralizing antibodies to PDGF-AA, however, inhibited only 10-40% of delayed TGF-beta-induced growth. Co-treatment with TGF-beta transiently delayed epidermal growth factor (EGF)-, basic fibroblast growth factor (bFGF)-, or PDGF-BB-induced entry into S phase but enhanced the delayed growth responses to these growth factors by 16.0-, 5.8-, or 4.2-fold, respectively. Neutralizing antibodies to PDGF-AA had no effect on these synergistic responses and exogenous PDGF-AA did not increase growth responses to EGF, bFGF, or PDGF-BB. In summary, TGF-beta induces marked delayed growth responses, alone and in combination with EGF, bFGF or PDGF-BB, that are largely independent of PDGF-AA.
GPs and consultants should work together in one stop health centres
Authors: Oona Mashta
Journal: BMJ (2007)

GPs should work alongside consultants in health centres providing a “one stop service” for patients to get treatment and tests in a single visit, says the UK government's GP tsar. 

Specially trained GPs could refer patients to senior consultants who are literally down the corridor, operating on cataracts, hernias, and varicose veins, for example, reducing hospital waiting times and saving money, David Colin-Thome, national director for primary care, recommends in the latest report on reconfiguring services. 

Dr Colin-Thome makes the clinical case for expanding the services provided by GPs, nurses, and pharmacists in the report, which is in line …
UK GPs vote against taking back responsibility for out of hours care
Authors: G. Iacobucci
Journal: BMJ (2013)

UK general practitioners (GPs) have overwhelmingly rejected a call to consider taking back 24 hour responsibility for out of hours medical provision, following a debate at the annual conference of local medical committees in London.

In an emergency debate announced to discuss health secretary Jeremy Hunt’s proposed changes to out of hours care, representatives were asked to consider a motion accepting that GPs should take back responsibility if important guarantees were met, including all funding from the NHS 111 urgent care helpline being transferred to out of hours care, and private companies being blocked from running services.

But the motion was overwhelmingly defeated after a succession of impassioned speeches from the floor, in …
Poisoning by Dieffenbachia
Authors: Richard W. Pohl
Journal: JAMA (1961)

ABSTRACT To the Editor:— Dieffenbachia is a small genus of tropical plants belonging to the Araceae, a family which also includes such common ornamental plants as the jack-in-a-pulpit, Philodendron, Pothos, Anthurium, calla lily, and Monstera. Many of these plants are shade-loving and have thick, waxy, resistant leaves and are therefore popular as house plants. Dieffenbachia plants are tall, reaching a height of 4 to 8 feet. The fleshy stems are as much as an inch thick, with conspicuous joints. They may be green or somewhat striped with white. The alternate leaves are stalked, and have dark green, ovate blades, up to 12 to 18 inches long, sometimes splashed with white markings.The common name of the genus, dumb cane, arises from the fact that ingestion of portions of the stem causes extreme irritation of the mouth and throat, with paralysis of the vocal cords. The inflammation and irritation may be prolonged.
AMPUTATION OF THE PENIS, FOLLOWED BY MULTIPLE PREGNANCY IN THE WIFE.
Authors: R. HARVEY REED
Journal: JAMA (1902)

Three years ago, J. K., a Finlander, aged 35, was admitted to the Wyoming General Hospital for disease of the penis. I was obliged to amputate the organ, leaving a stump after recovery of about one inch in length. Approximately one year after his discharge from the hospital, his wife, a small, healthy Finlander, of some 30 years, gave birth to a healthy male child. Being somewhat suspicious that the child might be illegitimate, I questioned the wife very closely, and was doubly assured that such was not the case, but a legitimate product of her husband. About one year later, she had a miscarriage, which was followed by metritis, which I treated with every indication of permanent relief. On April 1, 1902, I was called to see her and found that she was suffering from a threatened miscarriage. On April 6, I delivered her of a five months' fetus.
TEN-YEAR TRENDS OF PREDIABETES AND PREHYPERTENSION AMONG HEALTHY WOMEN: ANALYSIS OF NATIONAL HEALTH AND NUTRITIONAL EXAMINATION SURVEYS 2001-10
Authors: Saurabh Aggarwal, Navdeep Gupta, Rohit Loomba, Sandeep Khosla, Rohit Arora
Journal: Journal of the American College of Cardiology (2013)
Botulinum Toxin for Cricopharyngeal Dysfunction in Parkinson's Disease
Authors: Domenico A. Restivo, Agostino Palmeri, Rosario Marchese-Ragona
Journal: New England Journal of Medicine (2002)

To the Editor: Dysphagia occurs in more than 50 percent of patients with Parkinson's disease.1 Although all the phases of swallowing can be involved, dysphagia due to hyperactivity of the upper esophageal sphincter is the prevalent abnormality.1 Dysphagia does not respond to dopaminergic therapy.1 Surgical myotomy of the cricopharyngeal muscle is the treatment of choice for hyperactivity of the upper esophageal sphincter due to neurologic disorders,2 including Parkinson's disease.3 However, cricopharyngeal myotomy requires general anesthesia and is not always effective.2 Botulinum neurotoxin type A has been used to treat dysphagia.4,5 We describe its use in four patients (three men . . .
Modification of chemically induced diabetes in rats by vitamin E. Supplementation minimizes and depletion enhances development of diabetes.
Authors: A E Slonim, M L Surber, D L Page, R A Sharp, I M Burr
Journal: Journal of Clinical Investigation (1983)

Administration of the antioxidant vitamin E to rats, prior to administration of either streptozotocin or alloxan, provided protection against the diabetogenic effect of both these agents. This was demonstrated by their response to a glucose load, their pancreatic insulin content and light microscopy findings. In addition, rats whose antioxidant state was depleted, by being maintained on a vitamin E and selenium-deficient diet, demonstrated increased diabetogenic susceptibility to normally nondiabetogenic doses of streptozotocin. These findings provide indirect support for the suggestion that the chemical agents streptozotocin and alloxan may exert their diabetogenic effect by acting as oxidants or free radical producers.
Women Who Seek Therapeutic Abortion: A Comparison with Women Who Complete Their Pregnancies
Authors: CHARLES V. FORD, PIETRO CASTELNUOVO-TEDESCO, KAHLILA D. LONG
Journal: American Journal of Psychiatry (1972)

The authors compared 40 women seeking therapeutic abortion with 52 pregnant women who were not requesting abortion. The women in the abortion group complained more frequently of depression, anxiety, insomnia, loss of libido, anorexia, and suicidal ideation. Their average MMPI scores were significantly elevated for most scales. The women in the abortion group were more likely to have received psychiatric treatment, to have poorer sexual adjustment, and to reject the maternal role. The concept of "accidental" pregnancy is questioned, since women in both groups made little effort to prevent conception.
Patient-derived Granulocyte/Macrophage Colony–Stimulating Factor Autoantibodies Reproduce Pulmonary Alveolar Proteinosis in Nonhuman Primates
Authors: Takuro Sakagami, David Beck, Kanji Uchida, Takuji Suzuki, Brenna C. Carey, Koh Nakata, Gary Keller, Robert E. Wood, Susan E. Wert, Machiko Ikegami, Jeffrey A. Whitsett, Maurizio Luisetti, Stella Davies, Jeffrey P. Krischer, Alan Brody, Fred Ryckman, Bruce C. Trapnell
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibodies (GMAb) are strongly associated with idiopathic pulmonary alveolar proteinosis (PAP) and are believed to be important in its pathogenesis. However, levels of GMAb do not correlate with disease severity and GMAb are also present at low levels in healthy individuals.Our primary objective was to determine whether human GMAb would reproduce PAP in healthy primates. A secondary objective was to determine the concentration of GMAb resulting in loss of GM-CSF signaling in vivo (i.e., critical threshold).Nonhuman primates (Macaca fascicularis) were injected with highly purified, PAP patient-derived GMAb in dose-ranging (2.2-50 mg) single and multiple administration studies, and after blocking antihuman immunoglobulin immune responses, in chronic administration studies maintaining serum levels greater than 40 microg/ml for up to 11 months.GMAb blocked GM-CSF signaling causing (1) a milky-appearing bronchoalveolar lavage fluid containing increased surfactant lipids and proteins; (2) enlarged, foamy, surfactant-filled alveolar macrophages with reduced PU.1 and PPARgamma mRNA, and reduced tumor necrosis factor-alpha secretion; (3) pulmonary leukocytosis; (4) increased serum surfactant protein-D; and (5) impaired neutrophil functions. GM-CSF signaling varied inversely with GMAb concentration below a critical threshold of 5 microg/ml, which was similar in lungs and blood and to the value observed in patients with PAP.GMAb reproduced the molecular, cellular, and histopathologic features of PAP in healthy primates, demonstrating that GMAb directly cause PAP. These results have implications for therapy of PAP and help define the therapeutic window for potential use of GMAb to treat other disorders.
Response to Open Peer Commentaries on “‘Doctor, Would You Prescribe a Pill to Help Me … ?’ A National Survey of Physicians on Using Medicine for Human Enhancement”
Authors: Timothy D. Hotze, Kavita Shah, Emily E. Anderson, Matthew K. Wynia
Journal: The American Journal of Bioethics (2011)

Click to increase image sizeClick to decrease image size Acknowledgments The views expressed are those of the authors and should in no way be ascribed to the American Medical Association.
Trisomy 1q in polycythemia vera and its relation to disease transition
Authors: B. Swolin, A. Weinfeld, J. Westin
Journal: American Journal of Hematology (1986)

Clinical and cytogenetic details of 12 patients with polycythemia vera and complete or partial trisomy of the long arm of chromosome 1 are reported. All patients had trisomy for at least the segments 1q22 to 1qter. The 1q or material from 1q was translocated to another chromosome in eight patients. This was chromosome 9 in four patients, and those cases all had trisomy also for 9p. The trisomy 1q was found at the time of diagnosis in three patients, later during the polycythemic phase in five, and in four patients when they were first examined during a late stage of the disease. Acute leukemia or a myelodysplastic syndrome developed in eight of the 12 patients. Signs of advanced disease, eg, myeloid metaplasia or myelofibrosis, preceded the leukemia in four cases and was noted in one more patient. Trisomy 1q was the most frequent structural chromosome abnormality in patients with polycythemia vera. It is thus one of several nonrandom abnormalities that can appear at any stage of the disease. It seems to occur with higher frequency in patients with myelofibrosis and/or leukemia, but it is not a specific characteristic of these complications.