tbuckley/cabot-search huggingface dataset:
Points: Support received by carers of elderly dependants
Authors: J. M Kellett
Journal: BMJ (1985)

relatively little time available to talk to their inpatients because they are responsible for patients in several hospitals and are also concerned in work in the community, which may be particularly time consuming.Psychiatric firms usually have one junior trainee per site (or part ofone), and there are no housemen, so on call duties are shared by SHOs/registrars, whose posts usually coalesce to form training programmes involving enough firms and units to allow varied experience in a rotating scheme.Cuts in the numbers of junior psychiatric training posts are being proposed in many places and in some cases are draconian.If these numbers are reduced in this way without either a significant increase in consultant numbers or a commensurate increase in non-trainee junior posts then the standard of service may decline unacceptably in many places.Some regions err in supposing that manpower needs and use in psychiatry are essentially the same as in medical and surgical specialties.
Abstract 1078: ErbB/Pi3K signaling contributes to EGFR ligand expression in colorectal cancer cells
Authors: Bart Jacobs, Sabine Tejpar
Journal: Cancer Research (2012)

Abstract Background: Cellular expression of EGFR ligands is tightly regulated and is thought to be maintained by an autocrine signaling component in colorectal cancer cells. More importantly, the expression levels of individual ligands have gained recent interest since their expression of their mRNA was found to be linked to anti-EGFR therapy response. Since the expression of these ligands can be regulated by EGFR signaling elicited by EGF, we decided to investigate the contribution of MAPK as well as the PI3K axis, to EREG expression, in K-Ras wild-type colon cancer cells. Methods Colon cancer cells were used to interrogate EGFR downstream signaling. Several inhibitors targeting the ErbBs and the MAPK and PI3K/Akt pathways were used to dissect the pathways downstream of EGFR maintaining ligand mRNA levels in the lim1215 colon cancer cell line. Additionally, we used ER and AR reporter assays to selectively evaluate involvement of the EGFR pathway in transcriptional regulation of the pathway. Consequently, blockade and activation of EGFR pathway members was assessed by Western Blot. Results We show that Ereg and Areg mRNA levels are specifically maintained by erbb1 signaling. Treatment of lim1215 cells with inhibitors blocking Erbb1 (cetuximab) or ErbB1/Erbb2 (lapatinib) did results in near complete inhibition of Ereg and Areg expression in Kras/pi3K wild-type cells, while blockade of ErbB2 alone (which is activated in these cells) with Trastuzumab did not decrease Ereg nor Areg mRNA levels. Downstream of EGFR, we show that MEK signaling is not required for maintenance of EREG and AREG levels in lim1215 cells. Conversely, blockade of PI3K signaling by Akt inhibitors or PI3K inhibitors abolished EREG mRNA levels in these cells. This was reflected by the ability of overexpressed Akt to induce EREG and AREG reporter activity in 293T cells. In contrast, this activation could be rescued by the addition of Akt and PI3K inhibitors, but not MEK inhibitors in cellular media. Conclusions In this work we show that PI3K signaling is required for the transcription of EGFR ligands in colon cancer cells. In this regard, this provides additional insights to the recent findings that link PI3K/Akt signaling to Receptor Tyrosine Kinase expression and activation in cancer cells. Therefore, a global understanding of the signaling networks that control ligand availability and receptor abundance will be crucial in combining ErbB pathway inhibitors in the treatment of kras wild-type colon cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1078. doi:1538-7445.AM2012-1078
Reducing risks in gastroenterological practice
Authors: G NEALE
Journal: Gut (1998)

Eighty five malpractice claims against gastroenterologists have been analysed. Thirty seven (44%) arose from adverse events as a result of endoscopy and 48 (56%) from clinical practice. In 31 (84%) of the endoscopy cases (including all 13 endoscopic retrograde cholangiopancreatographies) there seemed to be significant fault. In nine cases the procedure was not clearly indicated and in 10 recognition and treatment of the adverse event was delayed. In no case had the patient given adequate informed consent. Diagnostic error was responsible for most of the claims related to clinical practice (31 of 48) of which 13 were indefensible. Failure to obtain an adequate history (17 cases) and insufficient awareness of disorders of the small intense (12 cases) were major factors. In 26 cases a key investigation was not performed. Seventeen claims were related to management or treatment but only one of these cases was difficult to defend. Overall, there was evidence of serious fault in 50% of claims. Greater care in selecting patients for endoscopic procedures and in providing postprocedural care would have eliminated the basis of more than half the claims arising from endoscopy. There would have been few claims if properly informed consent had been obtained. Over-ready acceptance of the diagnosis of a functional disorder (for example, irritable bowel, dyspepsia) was the usual cause of delays in diagnosis.
Molecular Aspects of Sickle Cell Hemoglobin: Clinical Applications
Authors: L. W. Diggs
Journal: JAMA (1971)

This book is welcomed because it brings under one cover the numerous recent contributions of Dr. Nalbandian and his associates relating to sickle cell diseases. The theme of the book is that the pathogenesis, diagnosis, and treatment have a molecular basis, that urea is capable of inhibiting and reversing the sickling process, and that urea is the treatment of choice. Murayama presents his hypothesis that the sickling process involves hydrophobic bonding between the hemoglobin molecules, resulting in the stacking of molecules in elongated microtubules. He discusses magnetically oriented sickled erythrocytes and the presence of a dialyzable cofactor. Marion Barnhart furnishes exquisite photographs of the three dimensional morphological features displayed by scanning electron microscopy and photographs of the internal structure of red cells revealed by high resolution transmission electron microscopy. Orten and Nalbandian present evidence that the electrophoretic mobility of sickle cell hemoglobin is not affected by urea. Henry collaborates in
Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection.
Authors: T Yoneda, M Urade, M Sakuda, T Miyazaki
Journal: Journal of Clinical Investigation (1986)

We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of 125I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound 125I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients.
Optimization of codon usage is required for effective genetic immunization against Art v 1, the major allergen of mugwort pollen
Authors: R. Bauer, M. Himly, A. Dedic, F. Ferreira, J. Thalhamer, A. Hartl
Journal: Allergy (2003)

As the major allergen of mugwort pollen, Art v 1 is an important target for specific immunotherapy. However, both recombinant protein as well as a gene vaccine for Art v 1 failed to be immunogenic in mice. In order to improve immunogenicity we focused on genetic immunization because interspecific differences of codon usage have been shown as an obstacle for effective induction of immune responses with gene vaccines encoding infectious pathogens.In order to find out, whether codon usage might also be used to improve genetic immunization with allergen genes, the response against a gene vaccine expressing the wild-type gene of Art v 1 (pCMV-wtArt) was compared with a synthetic codon-optimized vector with human codon usage (pCMV-humArt).Balb/c mice were injected intradermally with pCMV-wtArt or pCMV-humArt. In vitro expression levels of both constructs were compared in transfection experiments. Total immunoglobulin G (IgG), IgG1, IgG2a and IgE antibodies were analyzed by enzyme-linked immunosorbent assay and the anaphylactic activity of the sera was determined by allergen-specific degranulation of rat basophil leukemia-2H3 cells.No immune response was detectable with the gene vaccine expressing the wildtype Art v 1, but immunization with pCMV-humArt revealed a strong and allergen-specific induction of antibody responses. The antibodies recognized both the recombinant as well as the purified natural (glycosylated) Art v 1 molecule. The response type was Th1-biased, as indicated by high levels of IgG2a antibodies. Expression analysis with B16 mouse melanoma cells transfected with pCMV-humArt or pCMV-wtArt revealed an impaired expression of the wild-type vector but normal translation after recoding.The results demonstrate that optimization of codon usage offers a simple way to improve immunogenicity and therefore should be routinely considered in the development of gene vaccines for the treatment of allergy.
Prostaglandin H Synthase and Vascular Function
Authors: Sandra T. Davidge
Journal: Circulation Research (2001)

Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascular function. Under normal physiological conditions, PGHS-dependent vasodilators (such as prostacyclin) modulate vascular tone. However, PGHS-dependent vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH 2 ) predominates in some vascular pathologies (eg, systemic hypertension, diabetes, cerebral ischemia, and aging). This review will discuss the role of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for treatment of conditions such as chronic inflammatory disease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function.
How Best to Teach Women Breast Self-Examination
Authors: Suzanne W. Fletcher
Journal: Annals of Internal Medicine (1990)

Objective: To compare three methods for teaching breast self-examination. Design: Randomized controlled trial with factorial design. Setting: A general medicine group practice in a university hospital. Patients: Continuing-care patients from 40 to 68 years of age. Of 456 eligible women, 156 refused participation, 300 were randomly assigned, 269 completed assigned interventions, and 260 completed the post-test 1 year later. Interventions: One third of patients received nurse instruction stressing tactile skills (Mammacare group) (Mammatech Corporation, Gainesville, Florida); one third, traditional nurse instruction emphasizing technique (traditional group); and one third, no nurse instruction (control group). Half of each group received physician encouragement. Measurements and Main Results: One year later, women in the Mammacare group found more lumps (mean, 57%; 95% CI, 54% to 60%) in manufactured breast models than did those in the traditional (mean, 47%; CI, 44% to 51%) and control (mean, 45%; CI, 42% to 48%) groups. Lump detection specificity was unaffected. Self-reported examination frequency rose in all groups, to 5.1 times per 6 months in the traditional group, 4.2 in the Mammacare group, and 3.9 in the control group. Physician encouragement did not improve sensitivity, specificity, or overall frequency. Women in the Mammacare group used more of seven examination techniques (4.9) than did those in the traditional (3.9) or control (3.2) groups (P < 0.001). No group increased health care use or reported more overall worry about breast cancer. Conclusions: Mammacare instruction resulted in more long-term improved lump detection and examination technique use than did traditional instruction or physician encouragement. Breast self-examination instruction should emphasize lump detection skills.
Changing Times: Reflections on a Professional Lifetime: An Interview with Paul Beeson
Authors: Richard V. Lee
Journal: Annals of Internal Medicine (2000)

Paul Bruce Beeson is a child of the American frontier, the younger son of a dedicated general practitioner. Dr. Beeson's adventure was academic medicine; he studied at McGill University, the University of Pennsylvania, the Rockefeller Hospital in New York, and the Peter Bent Brigham Hospital in Boston. He became the Professor and Chair of the departments of medicine at Emory University and Yale University, and then, in Oslerian fashion, was appointed Nuffield Professor of Medicine at Oxford University. His legacy is his pupils, a Who's Who of 20th-century medicine. Dr. Beeson embodies the caring mission of medicine. He prefers to emphasize the patient–physician relationship and the social obligations of medicine; for example, Beeson was a founding member of Physicians for Social Responsibility. It seemed entirely appropriate that his memories and thoughts about 20th-century medicine, which he experienced and exemplified, should be a feature of the first issue of Annals in the year 2000.
Road to Euthanasia or Right to Refuse Care?-Reply
Authors: Robert W. Carton
Journal: JAMA (1990)

In Reply.—  Dr Sananman correctly points out that  whole-brain criterion of death has been accepted widely in  United States among medical professionals and state governments. However, to say this is not to exhaust  concept of death. There is a body of opinion that would define death as the loss of those brain functions that support awareness and cognition. 1,2 As a step in  direction of acceptance of this definition we note a growing tendency to withdraw life support from persons in  persistent vegetative state. 3 In this sense  range of those regarded as dead has widened.  The debate about  definition of death continues and will do so until in some way or another  technical criteria for determining death are derived from a broader philosophical concept of its meaning. 1-3
Adult‐onset cyclic neutropenia responsive to cyclosporine therapy in a patient with ankylosing spondylitis
Authors: Jan Storek, John A. Glaspy, Wayne W. Grody, Ellen Susi, Evan D. Slater
Journal: American Journal of Hematology (1993)

Abstract A 45‐year‐old female with a long history of HLA‐B27‐positive ankylosing spondylitis and ulcerative colitis developed cyclic neutropenia. She was hospitalized for high fever during each of three consecutive episodes of absolute neutropenia. On the third hospitalization, granulocyte‐colony‐stimulating factor (G‐CSF), 5 μg/kg/day, was given by subcutaneous injection and resulted in an increase of absolute neutrophil count from 0 to 2.2 × 10 9 /liter and an associated decrease of platelet count and hemoglobin as well as severe bone and joint pain predominantly in the middle and lower back and purulent diarrhea. The back pain necessitated discontinuation of the drug. Oral cyclosporine therapy was begun, and although the neutrophil count continued to oscillate, both the peaks and the nadirs were higher than previously, and symptoms of neutropenia subsided. We conclude that cyclosporine can be an effective treatment for cyclic neutropenia associated with autoimmunity since G‐CSF may cause exacerbations of autoimmune disorders.
Development of Intestinal Adenyl Cyclase and Its Response to Cholera Enterotoxin
Authors: Richard J. Grand, Frank M. Torti, Stephanie Jaksina
Journal: Journal of Clinical Investigation (1973)

Adenyl cyclase activity in intestinal membranes has been studied during development in the rabbit fetus from fetal day 17 to 10 days postnatally and in the human fetus from the 10th to the 17th wk of gestation. In the rabbit, the enzyme was already present by fetal day 17 and showed a fourfold peak rise in specific activity by 22 days. By 28 days, the specific activity had fallen toward adult levels and remained constant throughout gestation and the 1st wk of life. Fluoridestimulated activity showed a similar curve, and was 2.5-5 times the basal values. Activities in jejunum and ileum were comparable at all time points studied. Phosphodiesterase activity did not change during gestation. When fetal intestinal segments were incubated in vitro with purified cholera enterotoxin, adenyl cyclase activity in subsequently prepared membranes was increased two- to threefold. This level was not regularly further elevated by fluoride ion. Lithium ion inhibited both the basal and fluoride-stimulated enzyme activity in membranes prepared from rabbit fetuses at term. Lactase activity (reflecting the development of the microvilli) in either whole intestinal homogenates or in the membrane fractions showed a differnet pattern of development, with a rise beginning on fetal day 24 and a plateau just after birth. In intestinal membranes prepared from human fetuses, the activity of both basal and fluoride-stimulated adenyl cyclase tripled from the 10th to the 17th wk of gestation. The data both in the rabbit and in man show that intestinal adenyl cyclase is capable of responding to cholera enterotoxin quite early in gestation. In the rabbit, this occurs before the time of appearance or ville or of an enzyme marker (lactase) for microville. The results support the concept that adenyl cyclase is present in plasma membrane other than the brush border.
A Simple Maneuver to Treat Hiccups
Authors: Lawrence V. Perlman
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Recently a simple maneuver has been observed to end prolonged hiccupping in a dozen subjects. The individual is instructed to sit upright and to hold his breath. The patient then maximally extends his head for 10 to 15 seconds or as long as he can hold his breath. This maneuver tends to hold the diaphragm in a relatively fixed position particularly if the breath is held in inspiration. The mechanism appears to be the fixation of the anterior wall of the abdominal musculature which occurs when the head is hyperextended. Interference with diaphragmatic motion by this
The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders
Authors: N.C. COWLEY, P.M. FARR, S. SHUSTER
Journal: British Journal of Dermatology (1990)

Journal Article The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders Get access N.C. COWLEY, N.C. COWLEY Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.M. FARR, P.M. FARR Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Dr P.M. Farr. Search for other works by this author on: Oxford Academic Google Scholar S. SHUSTER S. SHUSTER Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 1, 1 January 1990, Pages 71–76, https://doi.org/10.1111/j.1365-2133.1990.tb08241.x Published: 01 January 1990
India issues new requirements for clinical trial approval
Authors: S. Bagcchi
Journal: BMJ (2014)

<h3>Summary</h3> Mutations in PINK1 causes autosomal-recessive Parkinson’s disease. Mitochondrial damage results in PINK1 import arrest on the Translocase of the Outer Mitochondrial Membrane (TOM) complex, resulting in the activation of its ubiquitin kinase activity by autophosphorylation and initiation of Parkin-dependent mitochondrial clearance. Herein we report crystal structures of the entire cytosolic domain of insect PINK1. Our structures reveal a dimeric autophosphorylation complex targeting phosphorylation at the invariant Ser205 (human Ser228). The dimer interface requires insert 2, which is unique to PINK1. The structures also reveal how an N-terminal helix binds to the C-terminal extension and provide insights into stabilization of PINK1 on the core TOM complex.
Women at double risk of small cell lung cancer
Authors: Z. Kmietowicz
Journal: BMJ (1998)

Women are nearly twice as likely as men to develop small cell lung cancer--which is the most aggressive form of the disease and which is often inoperable--according to the results of the largest study of patients with lung cancer yet to be carried out in the United Kingdom.

The clinical features of more than 1000 patients with lung cancer presenting to 46 UK hospitals have been analysed as part of a study based at the Royal College of Physicians' Research …
Putting the Public Back in Public Reporting of Health Care Quality
Authors: Tara Lagu, Peter K. Lindenauer
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal