tbuckley/cabot-search huggingface dataset:
Online Identities of Physicians
Authors: Bradley H. Crotty, Arash Mostaghimi, Vineet M. Arora
Journal: JAMA (2013)

ployed compared with those who did not deploy, this difference was not statistically significant (relative risk, 1.3; 95% CI, 1.0-1.7).The authors concluded that the increase in suicides paralleled an increase in mental disorder prevalence, mirroring our findings.Furthermore, the study did not control for covariates, particularly mental disorders.Suicidal behavior is extremely complex, and we agree with Drs Bryan and Clemans that other unmeasured factors may influence risk.It is important not to misinterpret our findings as suggesting that the conflicts in Iraq and Afghanistan have had no cumulative effect.Since 2005, suicide incidence in the Army increased just as sharply among soldiers who did not deploy as those who did.This corresponded to a steep increase in mental disorders in the military population overall, likely a product of intense wartime demands affecting soldiers throughout all phases of the deployment cycle.The aggregate research indicates that individuals who develop mental disorders following deployment or other military stressors unrelated to deployment will be at higher risk for suicide than individuals relatively less affected by such stressors.We agree that TBI is an important health concern requiring further study, along with other serious injuries and chronic illnesses associated with suicidal behaviors.5][6] With regard to potential moderators, stratification by age (<35 years and ≥35 years) did not change the results; deployment was not associated with increased risk for suicide in either age group.We took extensive steps to ensure valid results and address potential limitations of time-dependent covariates in the Cox models mentioned by Dr Larson and colleagues.This included adjusting for separation from the military and assessing deployment as both non-time-varying and timevarying covariates (in which individuals changed to a deployed status on the first day of deployment and remained in that category for the remainder of follow-up).The linkage of military and postmilitary data directly addresses potential biases of attrition from service.Most importantly, we conducted an entirely separate analysis using a nested casecontrol design with deployment as a static variable and found identical results.
Abstract 5378: Phase I trial of EUS-guided intratumoral vaccination with recombinant Panvac-F and systemic Panvac-V in patients with locally advanced pancreatic cancer
Authors: Elizabeth A. Poplin, David A. August, Tamir Ben-Menachem, Hazar Michael, Renee Artymyshyn, James L. Gulley, Jeffrey Schlom, Robert S. DiPaola, Edmund C. Lattime
Journal: Cancer Research (2012)

Abstract Preclinical studies in our laboratory were the first to demonstrate the superiority of intratumoral poxvirus vaccines in overcoming immune escape and effectively treating murine solid tumor models. Murine models of bladder and orthotopic mammary tumor demonstrated anergy to systemic immunization using antigen encoding vaccinia recombinants while responding to immunization into the tumor microenvironment. We present here the translation of these findings to a Phase I trial in six patients with locally advanced inoperable adenocarcinoma of the pancreas (NCT00669734). The first dose cohort of patients were treated using a combination of EUS-guided intrapancreatic tumor injection of recombinant Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM, 108 PFU) in addition to systemic Panvac-V (vaccinia, 2 X 108 PFU) and Panvac-F (109 PFU) boosts (accompanied by subcutaneous rH-GM-CSF, 100 mcg X 4 days). Patients received a total of 2 intrapancreatic injections of Panvac-F (2 weeks apart) with systemic Panvac-V and Panvac-F boosts given with GMCSF extending to day 71 (total of 2 intrapancreatic Panvac-F, 1 sc Panvac-V, 4 sc Panvac-F). Patients were allowed to transition to standard care at day 35. Patients were evaluated for toxicity, tumor progression, and serum CA 19-9 and CEA levels. Two of six patients were removed from study after approximately two weeks due to rapid disease progression and died one and six months after trial initiation. Of the remaining four, one had received prior treatment with gemcitabine followed by capecitabine and radiation and received no further treatment after vaccination; three received post-vaccination standard treatment with gemcitabine. Of the 4 patients with followup of greater than 6 mos, all have stable disease with no progression to metastasis (19 mos, 17 mos, 16 mos, 13 mos). One pt had a DLT (pancreatitis) that resolved allowing completion of protocol therapy. Results demonstrate that the “first in human” intrapancreatic administration of recombinant poxvirus was well tolerated with the complete regimen suggesting an encouraging period of stable disease. The trial is currently accruing patients at intrapancreatic dose level 2 (109 PFU). This study is supported by the NCI Cancer Therapeutics Evaluation Program (CTEP) and by NCI U01-CA07031 and P30-CA72720. 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 5378. doi:1538-7445.AM2012-5378
Countries should encourage use of generic substitutes, says OECD
Authors: J. Zarocostas
Journal: BMJ (2008)

More use of generic alternatives to off-patent drugs could ensure better value for money, says a study of drug pricing policies in rich countries. Such a policy would release resources and improve the availability of drugs to patients, the Organization for Economic Cooperation and Development (OECD) report says.

Several conditions are important to maximise the effect of generic substitute strategies: “Patients must be price sensitive, doctors and/or pharmacists must have incentives to prescribe or dispense cheaper drugs, and several generics qualified as substitutable for the originator must be available in the market.”

Such policies could …
Brain Tumor With Hyperosmolar Hyperglycemic Nonketotic Diabetic Coma
Authors: Ira. C. Denton
Journal: JAMA (1971)

To the Editor.—  A variety of neurological abnormalities are commonly observed in hyperosmolar hyperglycemic nonketotic (HHNK) states.1-4Coma is clinically the most representative of a spectrum of generally reversible neurological phenomena related to hypertonic hyperglycemia dehydration1of central nervous system (CNS) tissue. The expectation of neurological dysfunction attending the hyperosmolar syndrome, however, may reduce the clinician's suspicion of a coexisting primary CNS lesion.  This report concern a primary brain tumor in such a patient.  Report of a Case.—  A 54-year-old bachelor, who suffered a generalized seizure on the day of hospital admission, had been seen a week earlier because of stupor. At that time a mild right hemiparesis was reported. Polyuria ensued and the patient remained stuporous. This known hypertensive patient had remotely discontinued his antihypertensive medication and was not known to have taken any other.  The blood pressure was 100/40 mm Hg. He was markedly dehydrated and could
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Authors: Cristian A Lasagna-Reeves, Diana L Castillo-Carranza, Urmi Sengupta, Audra L Clos, George R Jackson, Rakez Kayed
Journal: Molecular Neurodegeneration (2011)

Abstract Background The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD) patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate. Results Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I), and activated caspase-9, which is related to the apoptotic mitochondrial pathway. Conclusions This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.
Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.
Authors: K Gyr, R Meier, J Haussler, P Bouletreau, W E Fleig, A Gatta, A Holstege, G Pomier-Layrargues, S W Schalm, M Groeneweg, G Scollo-Lavizzari, E Ventura, M L Zeneroli, R Williams, Y Yoo, R Amrein
Journal: Gut (1996)

Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE.To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease.49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study.Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement).The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated.A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.
Army general practitioner
Authors: J. Woodhouse
Journal: BMJ (1999)

BMJ Classified 18/25 DECEMBER 1999

Most newly vocationally trained general practitioners may wish to settle down into the practice of their dreams until retirement beckons, but some will want something different to do between finishing their vocational training scheme and drawing their pension. Although the days of serving all over the world are over, the army of the next century still offers plenty of variety. The strategic defence review led to the hospital based specialties largely being amalgamated into a tri-service organisation (navy, army, and air force combined), which is based near Portsmouth and in military wings attached to NHS hospitals near larger garrisons, but the general practitioners of each service still retain their single service identity. The army employs 220 uniformed general practitioners worldwide, with the option of serving in the Royal Army Medical Corps (RAMC) for anything from three years to 30 years.

Most army doctors join as sponsored or salaried medical students three years before finals under a system known as the cadetship scheme. At the end of their second year, after having contacted the RAMC Officers Recruitment Office, they and qualified doctors attend a familiarisation visit, where the process of mutual evaluation begins. After an interview and passing a medical examination they “sign up.” Female officers make up 25%of the initial intake, and ethnic minority doctors are well represented at 8%Until the recent European court ruling on gays in the military, it has been illegal to serve as a practising homosexual. It is too early to comment or whether this legislation will lead to a rise in homosexuality in the military medical community.

All new army doctors start a four month residential course—together with nurses, dentists, physiotherapists, vicars, vets, and lawyers—in Aldershot. Slowly the vagaries of army life, uniform, and surviving on the battlefield are unfolded so …
Proteinuria and Chronic Renal Disease.
Authors: Freddy F. Revilla
Journal: Annals of Internal Medicine (1968)

s1 May 1968Proteinuria and Chronic Renal Disease.Freddy F. Revilla, M.D., Carlos Marchena, M.D., E. Lovell Becker, M.D., F.A.C.P.Freddy F. Revilla, M.D.Search for more papers by this author, Carlos Marchena, M.D.Search for more papers by this author, E. Lovell Becker, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1183_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis study was undertaken to determine the types and clearances of various proteins found in the urine under three conditions: [1] in patients with gradually decreasing renal function, [2] in patients in whom renal disease is stable, and [3] in patients with nephrotic syndrome of the minimal or lipoid nephrosis type in whom proteinuria abates with treatment. In the first 2 groups there were 30 patients and in the third group, 5 patients. Glomerular filtration rate was determined by creatinine or inulin clearance, and glomerular selectivity of protein excretion was determined by an immunochemical precipitation technique relating the "clearance" of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Freddy F. Revilla, M.D.; Carlos Marchena, M.D.; E. Lovell Becker, M.D., F.A.C.P.Affiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1183-1183KeywordsCreatinineExcretionGlomerular filtration rateProteinsProteinuriaRenal diseasesUrine ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...
Correction of experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon.
Authors: P Puri, B O'Donnell
Journal: BMJ (1984)

Vesicoureteric reflux was produced in eight piglets by opening their bladders and slitting the anterior intravesical wall of the ureter. Cystography confirmed the presence of bilateral reflux in six piglets and unilateral reflux in two. Six to eight weeks later the bladder was again opened and Teflon paste injected in the space behind the intravesical ureter, thereby creating a support for the submucosal ureter. Cystography four to six weeks after injection of Teflon paste showed absence of reflux in all animals. Intravenous pyelography showed obstruction at the vesicoureteric junction in only one of the 14 treated ureters and this was later confirmed at necropsy. Animals were followed up from one to six months and then were killed. Gross examination of the vesicoureteric region showed a well circumscribed subureteric Teflon mass of firm consistency, retaining its shape and position at the site of the injection. Histological examination showed encapsulation of the implant by a thin layer of fibrous tissue and a foreign body granulomatous reaction with histiocytes and giant cells within the implant. Hence it is technically feasible to correct experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon paste--a relatively inert material. It may now be possible to treat vesicoureteric reflux in man by endoscopic injection of Teflon behind the intravesical ureter.
The Practitioner's Guide to Psychoactive Drugs
Authors: Howard A. Winkler
Journal: JAMA (1983)

ABSTRACT The Practitioner's Guide to Psychoactive Drugs, second edition, provides far more for the reader than the title suggests, and was a delight to read. In 12 sections it offers an enormous amount of valuable current information on some of the most frequently prescribed medications.A chapter on legal issues in prescribing psychoactive drugs not only informs the prescribing physician of the potential pitfalls, but is appropriate and timely in this era of increasing litigation.There are several features that I found to be particularly valuable and that enabled the reader to focus in on some of the more salient points in the text. These included highlighting sentences and paragraphs in darker print, which was eye catching. Another innovation was blocking out sections in shades of gray with clearly defined margins, permitting the reader a quick summary of the material under discussion. The authors make excellent use of charts and tables,
Mortality and the Length of Dialysis
Authors: Edward E. Berger
Journal: JAMA (1991)

"Mortality and Duration of Hemodialysis Treatment" by Held et al,<sup>1</sup>presented elsewhere in this issue, is noteworthy for three distinct reasons. Clinical nephrologists will be interested in the statistically robust association between short dialysis time and increased patient mortality. Other practitioners and researchers should note the value of retrospective analyses of large databases in revealing clinical relationships that may not be apparent through smaller, prospective clinical trials. Finally, social policy analysts ignore, at their peril, the demonstration of causal relationships among payment policy, clinical practice, and clinical outcome. The annual mortality rate among US dialysis patients increased steadily from 20.1% in 1983 to 24.3% in 1988, and is clearly the highest among developed nations.<sup>2,3</sup>At the same time, average treatment length has been decreasing. The National Cooperative Dialysis Study, a small but highly controlled prospective trial, showed that short dialysis length was a significant predictor of patient morbidity,
Climate change conference ends in recrimination
Authors: S. Kumar
Journal: BMJ (2002)

Two types of systems are used in ex vivo human placental perfusion studies to predict fetal drug exposures, that is, closed systems with recirculation of the maternal and fetal buffer and open systems using a single-pass mode without recirculation. The in vivo fetal/maternal (F:M) ratio of metformin, a cationic drug that crosses the placenta, is consistent with that reported in an open system ex vivo but not with that in a closed system. In the present study, we aimed to develop a pharmacokinetic (PK) model of transplacental transfer of metformin to predict in vivo fetal exposure to metformin and to resolve the apparent inconsistency between open and closed ex vivo systems. The developed model shows that the difference between open and closed systems is due to the difference in the time required to achieve the steady state. The model-predicted F:M ratio (approx. 0.88) is consistent with reported in vivo values [mean (95% confidence interval): 1.10 (0.69–1.51)]. The model incorporates bidirectional transport via organic cation transporter 3 (OCT3) at the basal plasma membrane, and simulations indicate that the use of trimethoprim (an OCT3 inhibitor) to prevent microbial growth in the placenta ex vivo has a negligible effect on the overall maternal-to-fetal and fetal-to-maternal clearances. The model could successfully predict in vivo fetal exposure using ex vivo human placental perfusion data from both closed and open systems. This transplacental PK modeling approach is expected to be useful for evaluating human fetal exposures to other poorly permeable compounds, besides metformin. <h3>SIGNIFICANCE STATEMENT</h3> We developed a pharmacokinetic model of transplacental transfer of metformin, used to treat gestational diabetes mellitus, in order to predict in vivo fetal exposure and resolve the discrepancy between reported findings in open and closed ex vivo perfusion systems. The discrepancy is due to a difference in the time required to reach the steady state. The model can predict in vivo fetal exposure using data from both closed and open systems.
Pediatric Sports Medicine for the Practitioner: From Physiologic Principles to Clinical Applications
Authors: Richard W. Newcomb
Journal: JAMA (1984)

Physicians who care for children are often called upon to render advice on sports and exercise. Long before the physical fitness fad struck the adult sector, children used sports to have fun, work off steam, test themselves against their peers, and learn about real life. Their physicians, once called on only to tend their wounds, now must be prepared to advise on exercise appropriate to age, size, development, and any concurrent disease, and to control access to many competitive activities. This well-written, carefully documented book provides a great deal of information by which such decisions can be informed. Its extended title accurately describes the focus of the book: exercise physiology in the immature human, with special applications to children with several forms of chronic disorders. Two initial chapters clearly describe the response of children of differing age, sex, and size to exercise. Applications to children with pulmonary, cardiovascular, endocrine, nutritional,
Many reports of RCTs give insufficient data for Cochrane reviewers
Authors: E H. Walters, J A E Walters
Journal: BMJ (1999)

EDITOR—We endorse the call in Editor's choice in the issue of 31 October for improvement in the performance of clinical trials. As part of the Cochrane Airways Group we are carrying out a systematic review of trials on the use of β agonists in asthma. In many of our selected publications we have found it difficult to tell whether allocation of treatment was adequately concealed.

The reviews undertaken for the Cochrane Collaboration …
Trastuzumab Therapy for Tamoxifen-Stimulated Endometrial Cancer
Authors: Clodia Osipo, Kathleen Meeke, Hong Liu, Dong Cheng, Sherry Lim, Alyssa Weichel, V. Craig Jordan
Journal: Cancer Research (2005)

Abstract A novel in vivo model of tamoxifen-stimulated endometrial cancer was developed and the role of HER-2/neu investigated by using trastuzumab. Tamoxifen-stimulated tumors (ECC-1TAM) were growth stimulated by 17β-estradiol (E2), tamoxifen, or raloxifene. Trastuzumab inhibited growth of E2-stimulated ECC-1E2 tumors by 50% and tamoxifen-stimulated ECC-1TAM tumors by 100%. ECC-1 tumors expressed functional estrogen receptor α (ERα) as measured by induction of pS2 and c-myc mRNAs. E2 induced pS2 and c-myc mRNAs up to 40-fold in ECC-1E2 and ECC-1TAM. Tamoxifen induced pS2 and c-myc mRNAs up to 5-fold in ECC-1E2 tumors and up to 10-fold in ECC-TAM tumors. Trastuzumab blocked E2-induced pS2 mRNA (P &amp;lt; 0.01) in ECC-1E2 by 50% and tamoxifen-induced c-myc mRNA (P &amp;lt; 0.1) in ECC-1TAM tumors by 70%. Trastuzumab decreased phosphorylated and total HER-2/neu protein in ECC-1E2 and ECC-1TAM tumors. However, only phospho-ERK-1/2 and not phospho-Akt protein was decreased by trastuzumab in tamoxifen-treated ECC-1TAM tumors. The insulin-like growth factor (IGF-I) signaling pathway also activates extracellular signal-related kinase (ERK)-1/2 and could block the efficacy of trastuzumab in ECC-1E2 tumors. The results showed that IGF-I, IGF-IR mRNAs, and phospho-insulin receptor substrate-1 (IRS-1) protein were decreased in ECC-1TAM compared with ECC-1E2 tumors. The results show that trastuzumab is an effective therapy for both E2-stimulated and tamoxifen-stimulated endometrial cancer. The data suggest estrogenic activities of E2 and tamoxifen at ERα-regulated pS2 and c-myc genes are in part mediated by HER-2/neu. However, trastuzumab is a better growth inhibitor of ECC-1TAM tumors where there is diminished IGF-I signaling allowing for complete blockade of the downstream phospho-ERK-1/2 signal.