tbuckley/cabot-search huggingface dataset:
Care of chronic psychotics.
Authors: M Z Hussain, A G Khan
Journal: BMJ (1971)

action of agents capable of reacting with cellular DNA.Recently the isolation3 of a DNA polymerase-deficient (pol A7) strain has permitted the verification of this prediction.2 4 In the present study the sensitivity of such a mutant to gentian violet and related dyes was examined.TABLE.-Effect of agents on the growth of a DNA polymerase-deficient strain of E. coli Diameter of zone of inhibition (mm) Agent Parent Strain Mutant Strain Colistin (polymyxin F) 14 14 Kanamycin 24 25 Neomycin 22 22 Streptomycin 19 19 Ampicillin
Web Searching for Information About Physicians
Authors: Tristan Gorrindo
Journal: JAMA (2008)

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
Princes and Peasants: Smallpox in History
Authors: Lester S. King
Journal: JAMA (1984)

In all of medical history, one of the most dramatic episodes is the eradication of smallpox. The disease has a fascinating history. It was sufficiently distinctive so that even ancient accounts provided fairly reliable information for the historian. Dr Hopkins, with enormous acumen and diligence, has traced the impact that smallpox has had in human history and, although with lesser emphasis, the way that modern science has conquered it. There is considerable difference between "smallpox in history" and "history of smallpox." They are not synonymous. Hopkins has given us a quite exhaustive account of the former. The disease, appearing in epidemics, wrought enormous changes. Conventional history, dealing with wars and dynasties and the dominant classes, tells us how the deaths and illnesses of rulers and princes affected the course of nations. The more progressive types of history, dealing with social problems and economic events, show the effects of epidemics on
Abstract 2345: Combined inhibition of protein kinase C and MEK is a rational therapeutic approach for melanomas with GNAQ or GNA11 mutations.
Authors: Xu Chen, Qiuxia Wu, Boris C. Bastian
Journal: Cancer Research (2013)

Abstract Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. There currently is no effective treatment for metastatic UM. UM differs from cutaneous melanoma in that it lacks BRAF, NRAS, or KIT mutations but instead harbors mutations in the Gαq family members GNAQ and GNA11 in over 80 to 90% of cases. Understanding the downstream effector pathways of these oncoproteins is of considerable interest to identify opportunities for targeted therapy. Using 293T cells, immortalized mouse and human melanocytes, we find that GNAQQ209L or GNA11Q209L induce activation of the protein kinase C (PKC) and MAPK pathways. ShRNA mediated knock-down of mutant GNAQ abrogates both PKC and MAPK activation in human melanoma cell lines or model systems. Using two different PKC inhibitors we found selective extinction of PKC and MAPK signalling and induction of G1 arrest in panels of melanoma cell lines carrying GNAQ or GNA11 mutations, whereas no such effect was observed in melanoma cell lines with other mutations. MAPK activation occurred downstream of activated PKC in cells with GNAQ or GNA11 mutations. In contrast to PKC inhibitors, which selectively inhibited the growth of melanoma cell lines with GNAQ or GNA11 mutations, the MEK inhibitor PD0325901 inhibited melanoma cell lines irrespective of their GNAQ/11 mutation status. In vivo the PKC inhibitor AEB071 slowed the growth of tumors in an allograft model of GNAQQ209L transduced melanocytes, but did not induce tumor shrinkage. Analysis of tumor lysates identified suppression of PKC signaling but not of MAP-kinase pathway signaling under chronic PKC inhibition. The rebound of MAP-kinase activation could be overcome using a combination of AEB071 with the MEK inhibitor PD0325901, which showed strong synergy in halting proliferation and in inducing apoptosis. Our data suggest that PKC is a rational therapeutic target for melanoma patients with GNAQ or GNA11 mutations and indicate that a combination therapy with MEK inhibitor is superior to treatment with either approach alone. Citation Format: Xu Chen, Qiuxia Wu, Boris C. Bastian. Combined inhibition of protein kinase C and MEK is a rational therapeutic approach for melanomas with GNAQ or GNA11 mutations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2345. doi:10.1158/1538-7445.AM2013-2345
The Physician and Cost Containment
Authors: Larry R. Kirkland
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Inspired by the article "The Physician's Role in the Cost-Containment Problem" by Dresnick and colleagues (241:1606, 1979), data from a similar study are submitted. In February 1978, a questionnaire was sent, with a return envelope, to each of the 158 physicians on the staff or admitting lists of Emory University Hospital, Atlanta. Each recipient was asked to list the tests (and their charges) that were routinely part of the "admissions package" on his service. Reading and completing the form took approximately 60 s. Despite this, only 66 forms were returned. There are several points of interest: Although our questionnaire was shorter than that of Dresnick et al, our response rate (42%) was close to their 36% return from full-time faculty. Our response rates were similar for internal medicine (47%), surgery (49%), and other clinical services (45%). However, nonclinical services, eg, radiology, returned only 15% (four
Provision of hearing aids: Does specialist assessment cause delay?
Authors: A. Harris
Journal: BMJ (1989)

family to be in excess of that in his two brothers.We counted all moles (incluiding those <3 mm and ¢3 mm diameter) in the patient, his identical twin, and his other brother aged 16 years (table) and observed an excess of moles in the patient.All three brothers had identical skin types and had had the same lifestyle and exposure to sun in that all had spent their earl childhood in Germanx, four weeks in Hong Kong and two weeks in Spain, but the rest of their lives in the United Kingdom.Nu mbers oJ moles in the threev siblitlgs Patient Idenitical twin Brother
Hyperglycaemia in acute coronary syndromes: summary of NICE guidance
Authors: A. Senthinathan, V. Kelly, M. Dzingina, D. Jones, M. Baker, D. Longson
Journal: BMJ (2011)

Hyperglycaemia is common in patients who are admitted to hospital with acute coronary syndrome. In the Euro Heart Survey on diabetes, 22% of people admitted to hospital as emergency cases because of coronary artery disease were found to have undiagnosed diabetes after a glucose tolerance test, with a further 36% found to have impaired glucose tolerance.1 Hyperglycaemia is a powerful predictor of poorer survival and increased risk of complications while in hospital.2 3 Despite this, hyperglycaemia remains under-recognised as a risk factor for acute coronary syndrome and is often untreated.4 This article summarises the recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of hyperglycaemia within the first 48 hours of a patient's admission to hospital for acute coronary syndrome.5 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Managing hyperglycaemia in inpatients within 48 hours of acute coronary syndrome
The killing of doctors in Iraq must stop
Authors: Nisreen A Alwan
Journal: BMJ (2011)

On 29 March 2011 Professor Mohammed Alwan, dean of Al - Mustansiriya Medical School in Baghdad and my uncle, was assassinated. A bomb was planted in his car and exploded as he got in after leaving his medical practice. He was a distinguished academic and surgeon who was respected by his students, and he was a fellow of the Royal College of Surgeons of England. Within a week, another clinical academic from the same institution—Dr Zaid Abdul Munim, head of research at the molecular department—was killed with a similar technique.

These are not isolated incidents. Assassinations and kidnapping of Iraqi doctors, academics, and scientists are now part of everyday life in Iraq, particularly in Baghdad. This phenomenon started after the 2003 US led invasion of the country. One study estimated the combined rate of violent event (death, kidnapping, and threats) among specialist doctors in Iraq in 2004-7 to …
Renal Tubular Sites of Altered Calcium Transport in Phosphate-depleted Rats
Authors: Kai Lau, Zalman S. Agus, Martin Goldberg, Stanley Goldfarb
Journal: Journal of Clinical Investigation (1979)

Increased calcium (Ca) excretion is characteristic of chronic phosphate (PO4) depletion (PD). To study the changes in tubular transport and the site of the hypocalciuric effect of PO4 administration, clearance and micropuncture experiments were performed in intact rats pair fed either a control diet (0.5% PO4) or a PO4-depleted (PD) diet (0.01% PO4) plus Al(OH3) and in parathyroidectomized (PTX) PD rats, infused either with saline or with neutral sodium PO4.
S71 Computer-Guided consultation in COPD practice
Authors: E B Thompson, M G Pearson, L Davies, E McKnight, A Trusdale, K Sargeant, R M Angus
Journal: Thorax (2013)

<h3>RATIONALE</h3> We previously showed a comprehensive computer guided-consultation (containing prompts developed from NICE guidelines) in COPD primary care was feasible without specialist training, while preserving the autonomy of clinical decision making. The pilot study based on COPD primary care register, 88% had a proposed management change and 29% of patients had a diagnostic revision. We have re-examined the impact in real life to determine if this is repeated. <h3>Methods</h3> We report on review of 2000 patients drawn from COPD registers across 78 practices. 459 (23%) did not have COPD based on spirometry. 1541 with COPD, had a mean (SD) age of 69.4 (9.8) yrs, 903 (58.6%)male, 1407 (91.6%) had been smokers and 597 (38.4%) were current smokers. The mean (SD) FEV1 was 1.48 (0.56) with a mean FEV1 percent predicted of 61.4 and a mean FEV1/FVC ratio of 52.4. The mean (SD) MRC score was 2.58 (0.9) and BMI was 27.0 (5.9). <h3>Results</h3> Treatment modifications were implemented across various interventions. Pharmacological recommendations included the addition of: Short-acting bronchodilator in 75/1541 (4.9%), and a long-acting bronchodilator (LAMA) in 78/1541 (5.1%). Long-acting beta agonist/inhaled corticosteroid combination (LABA/ICS) was added in 75 patients including 37 with only moderate disease. In 32 (1.8%) patients the recommendation was to discontinue various inhaled medication and in 28 (1.6%) patients these were LABA/ICS combinations. In addition, 28.8% of patients currently smoking, accepted referral for smoking cessation support. 38 patients had hypoxia, 10 already on oxygen, and 4/28 (14.3%) referred for oxygen assessment. 33.3% of eligible patients were referred to pulmonary rehabilitation. 77.5% required and were provided with a written educational pack, and a formal crisis management plan formulated for 49.3% cases. Inhaler technique was inadequate in 10.2% of patients and in part drove the prescribing changes. <h3>Conclusion</h3> Using computer guiding consultation in real life practice resulted in substantial management recommendations and diagnostic revisions. COPD care can be improved, using computer guided consultation which enables non specialists to achieve it.
Changes in the expression of methionine adenosyltransferase genes and S-adenosylmethionine homeostasis during hepatic stellate cell activation
Authors: Komal Ramani, Heping Yang, John Kuhlenkamp, Lauda Tomasi, Hidekazu Tsukamoto, José M. Mato, Shelly C. Lu
Journal: Hepatology (2009)

Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Methionine adenosyltransferase (MAT) catalyzes biosynthesis of S-adenosylmethionine (SAMe), the principle methyl donor. SAMe metabolism generates two methylation inhibitors, methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH). Liver cell proliferation is associated with induction of two nonliver-specific MATs: MAT2A, which encodes the catalytic subunit α2, and MAT2β, which encodes a regulatory subunit β that modulates the activity of the MAT2A-encoded isoenzyme MATII. We reported that MAT2A and MAT2β genes are required for liver cancer cell growth that is induced by the profibrogenic factor leptin. Also, MAT2β regulates leptin signaling. The strong association of MAT genes with proliferation and leptin signaling in liver cells led us to examine the role of these genes during HSC activation. MAT2A and MAT2β are induced in culture-activated primary rat HSCs and HSCs from 10-day bile duct ligated (BDL) rat livers. HSC activation led to a decline in intracellular SAMe and MTA levels, a drop in the SAMe/SAH ratio, and global DNA hypomethylation. The decrease in SAMe levels was associated with lower MATII activity during activation. MAT2A silencing in primary HSCs and MAT2A or MAT2β silencing in the human stellate cell line LX-2 resulted in decreased collagen and alpha-smooth muscle actin (α-SMA) expression and cell growth and increased apoptosis. MAT2A knockdown decreased intracellular SAMe levels in LX-2 cells. Activation of extracellular signal-regulated kinase and phosphatidylinositol-3-kinase signaling in LX-2 cells required the expression of MAT2β but not that of MAT2A. Conclusion: MAT2A and MAT2β genes are induced during HSC activation and are essential for this process. The SAMe level falls, resulting in global DNA hypomethylation. (Hepatology 2010.)
804. HSVtk Mediated Immunostimulatory Tumor Cell Killing Enhances Adoptive T Cell Therapy in a B16 Melanoma Model
Authors: Luis Sanchez-Perez, Michael Gough, Jian Qiao, Uma Thanarajasingam, Atique Ahmed, Rosa Maria Diaz, Richard Vile
Journal: Molecular Therapy (2005)

Top of pageAbstract
Many cancer gene therapy strategies rely upon the ability to deliver genes to tumors in vivo leading to the direct killing of tumor cells. We have shown previously, using the B16/HSVtk melanoma model, that in situ tumor cell death can be immunogenic due to recruitment, loading and activation of antigen presenting cells with released tumor antigens. We have now focused upon combining gene therapy with other therapeutic modalities to increase the efficacy of either alone in an attempt to compensate for the poor efficiency of gene delivery. Therefore, we have studied the effects of killing tumors with the HSVtk system to generate an inflammatory environment in vivo to enhance the recruitment of adoptively transferred T cells to the tumor site. B16 melanoma cells expressing the model antigen chicken ovalbumin were engineered to stably express HSVtk by retrovirus infection. In vivo GCV treatment of mice bearing B16ovaHSVtk tumors resulted in intratumoral expression of IL-12, IFN-|[gamma]| and TNF|[alpha]|, amongst other cytokines. Tumors treated with GCV accumulated increased percentages of NK1.1+ and Ly6G+ cells over PBS control. Suboptimal numbers of adoptively transferred ova-specific activated CD8+ T cells, along with GCV therapy, in tumor bearing mice resulted in complete tumor regressions in a dose dependent manner, where neither of the therapies alone was curative. NK cells were necessary for the efficacy of the therapy since NK cell depleted mice did not benefit from GCV treatment plus adoptive transfer. Interestingly, in vitro treatment of B16ovaHSVtk cells with TNF|[alpha]| and IFN-|[gamma]| enhanced GCV mediated cell killing, suggesting that the cytokines induced intratumorally upon in vivo GCV treatment of B16ovaHSVtk tumors play a significant role in tumor regression. These studies indicate that the local inflammatory reaction induced by achieving only limited tumor cell killing by HSVtk gene transfer can be exploited therapeutically by the combination with adoptive transfer of antigen specific T cells. The efficacy of this therapy relies on the dose and timing of the adoptive transfer as well as on host NK cells, and, probably, intratumoral cytokines. These results emphasize the importance of the immune mediated bystander effects of HSVtk-mediated tumor cell killing for the success of suicide gene therapy in vivo, and indicate that adoptive transfer of antigen specific activated T cells, in combination with HSVtk/GCV gene therapy, offers a novel combination approach for cancer therapy.
Influenza vaccination: policy versus evidence
Authors: Tom Jefferson
Journal: BMJ (2006)

Schizophrenia and its subtypes are part of a complex brain disorder with multiple postulated aetiologies. There is evidence that this common disease is genetically heterogeneous, with many loci involved. In this report, we describe a mother and daughter affected with schizophrenia, who are carriers of a t(9;14)(q34;q13) chromosome. By mapping on flow sorted aberrant chromosomes isolated from lymphoblast cell lines, both subjects were found to have a translocation breakpoint junction between the markers D14S730 and D14S70, a 683 kb interval on chromosome 14q13. This interval was found to contain the neuronal PAS3 gene (<i>NPAS3</i>), by annotating the genomic sequence for ESTs and performing RACE and cDNA library screenings. The <i>NPAS3</i> gene was characterised with respect to the genomic structure, human expression profile, and protein cellular localisation to gain insight into gene function. The translocation breakpoint junction lies within the third intron of <i>NPAS3</i>, resulting in the disruption of the coding potential. The fact that the bHLH and PAS domains are disrupted from the remaining parts of the encoded protein suggests that the DNA binding and dimerisation functions of this protein are destroyed. The daughter (proband), who is more severely affected, has an additional microdeletion in the second intron of <i>NPAS3</i>. On chromosome 9q34, the translocation breakpoint junction was defined between D9S752 and D9S972 and no genes were found to be disrupted. We propose that haploinsufficiency of <i>NPAS3</i> contributes to the cause of mental illness in this family.
Suspected contamination leads to recall of meningitis C vaccine
Authors: C. White
Journal: BMJ (2009)

Two batches of meningitis C vaccine distributed to general practices across England have been recalled by the medicines watchdog amid fears that they may have been contaminated.

The manufacturer, Novartis Vaccines, raised the alarm last week after routine sampling of a shipment of doses from the same two batches air freighted to the United States showed contamination with Staphylococcus aureus .

The sterility of the solvent, aluminium hydroxide, which is used to mix the vaccine, had been compromised.

In all 61 117 doses of meningitis C vaccine (Menjugate Kit) were sent to the UK, of which 17 000 …
41. Evaluation of Lung Cancer Virotherapy with Oncolytic Semliki Forest Virus Using Immunodeficient Rodent Tumor Model
Authors: Ann-Marie Määttä, Tiina Wahlfors, Katja Häkkinen, Linda Jansson, Markus Vähä-Koskela, Ari Hinkkanen, Kimmo Mäkinen, Jarmo Wahlfors
Journal: Molecular Therapy (2006)

Virotherapy has been postulated as a promising approach for killing tumor cells. Unlike conventional gene therapy, it uses replication competent viruses that are able to spread through tumor tissue and replicate in cancer cells, eventually causing destruction of the tumor. Most of the virotherapy studies are focused on oncolytic adenoviruses, but in this study we wanted to evaluate the efficacy of replication competent alphavirus, Semliki forest virus (SFV) strain A7 (74). It is not considered a human pathogen and also, it causes only transient and benign CNS infection to adult mice. To test the efficacy of SFV A7 (74) virotherapy, we first conducted in vitro studies with different (A549, NCI-H661 and SW900) human non small cell lung cancer (NSCLC) cell lines representing all the three main types of NSCLC. The aim was to determine, how extensively different amounts (MOI 0.1, 1 and 10) of virus destroy the target cells. After in vitro studies we determined the efficacy of the virotherapy in vivo (in immunodeficient NMRI nu/nu mice) using a subcutaneous A549 tumor model. In this experiment we compared the efficacy of virotherapy when SFV A7 (74) virus was injected systemically (i.v. and i.p.) or locally (i.t.). Virus distribution analysis (serum, brain and tumor tissues) was carried out 16 h, 2 days, 4 days and one week after viral injections. SFV A7 (74) virotherapy appeared to be very efficient in vitro, inducing in all NSCLC cell lines almost 100% cell death 48 h after infection. In subcutaneous (lung adenocarcinoma A549) tumor model, the therapeutic efficacy was better when virus was injected locally. With this approach, the tumor growth rate was reduced significantly when compared to control group. When virus was administered systemically, the tumor growth was delayed, but the tumors reached the same size as the control tumors by the end of the experiment. The distribution study showed the neurotrophic nature of the Semilki forest virus: 7 days post-infection the virus was found in the brain, but not in serum or in tumors. However there were no differences in the behaviour or overall condition of SFV A7 (74) - treated mice and control mice. Even though the study was done with an immunocompromized mice model (lack of T cell response), our results suggest that the animals were able to elicit at least a partial immune response against the virus. This was seen particularly with the systemic delivery route: viruses did not find the tumors efficiently and were unable to initiate powerful intratumoral replication. Thus, to obtain high therapeutic efficacy with SFV virotherapy, the route of virus administration and the immunogenicity of the virus should be carefully evaluated.