tbuckley/cabot-search huggingface dataset:
Pertuzumab and Trastuzumab: Re-Responses to 2 Biological Agents in Patients with HER2-Positive Breast Cancer Which Had Previously Progressed during Therapy with Each Agent Given Separately: A New Biological and Clinical Observation.
Authors: J. Baselga, J. Cortes, P. Fumoleau, T. Petrella, K. Gelmon, S. Verma, X. Pivot, G. Ross, T. Szado, L. Gianni
Journal: Cancer Research (2009)

Abstract Background: Pertuzumab, a fully humanised IgG1 monoclonal antibody, is a human epidermal growth factor receptor 2 (HER2)-dimerisation inhibitor directed to the dimerisation epitope of HER2 (trastuzumab binds to the juxta-membrane epitope). Pertuzumab has demonstrated promising activity when given with trastuzumab to patients with HER2-positive metastatic breast cancer (mBC) which had progressed during therapy with trastuzumab in a 2-step Phase II study.1Methods: The protocol was amended to include a 3rd cohort of patients to determine the activity of pertuzumab when given without trastuzumab.2 Patients recruited into this 3rd cohort were allowed to have trastuzumab re-introduced in combination with pertuzumab if there was inadequate response to pertuzumab alone or response followed by relapse.Results: Twenty-nine patients were recruited into this 3rd cohort. Patients had reached their 3rd line of treatment for mBC. To date, 15 patients have had trastuzumab re-introduced after disease progression on trastuzumab therapy and pertuzumab monotherapy. Among these 15 patients, at the time of this analysis there have been 3 patients with confirmed responses. There are also 4 patients who had not yet undergone 8 cycles of assessments to reach the overall best response end point, of which at least 2 were experiencing stablisation of disease. Updated data on activity and toxicity will be presented.Conclusions: We believe this is the first time that anti-tumour activity has been reported in patients when 2 biological agents have been used together after the disease has progressed during therapy with each agent alone. There are several mechanisms which might explain this phenomenon. Trastuzumab prevents proteolytic cleavage of the extracellular domain of HER2, keeping the receptor in situ. The addition of a second antibody to a separate epitope increases the potential for antibody-dependent cell-mediated cytotoxicity and prevents dimerisation between HER2 and other HER family members, such as HER1 and HER3. The combined antibodies might increase the efficiency of inhibition of signal transduction. There are wide-ranging and potentially significant biological and clinical implications. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5114.
Residency Training and International Medical Graduates
Authors: Giovanni Traverso, Graham T. McMahon
Journal: JAMA (2012)

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
Neuropsychologic effects of long-term exposure to pesticides: results from the French Phytoner study.
Authors: I Baldi, L Filleul, B Mohammed-Brahim, C Fabrigoule, J F Dartigues, S Schwall, J P Drevet, R Salamon, P Brochard
Journal: Environmental Health Perspectives (2001)

The Phytoner study investigated a possible association between neuropsychologic performances and long-term exposure to pesticides in Bordeaux vineyard workers, most of whom use fungicides. Among the 917 subjects interviewed from February 1997 to August 1998, 528 were directly exposed to pesticides through mixing and/or spraying (mean exposure duration: 22 years), 173 were indirectly exposed through contact with treated plants, and 216 were never exposed. All subjects performed neuropsychologic tests administered at home by trained psychologists. The risk of scoring a low performance on the tests was constantly higher in exposed subjects. When taking into account educational level, age, sex, alcohol consumption, smoking, environmental exposures, and depressive symptoms and when restricting analysis to subgroups, results remained significant for most tests, with odds ratios (OR) exceeding 2. These results point to long-term cognitive effects of low-level exposure to pesticides in occupational conditions. Given the frequency of pesticide use and the potential disabilities resulting from cognitive impairments, further toxicologic and epidemiologic research is needed to confirm these results and assess the impact on public health.
Dwarfism in the Pygmy
Authors: Thomas J. Merimee, Jürgen Zapf, E. Rudolf Froesch
Journal: New England Journal of Medicine (1981)

Insulin-like growth factors (IGFs) I and II, which are present in normal human beings, were measured in serum samples from 11 pygmies from the Central African Republic, 31 controls, and 12 patients with growth hormone deficiency. The mean serum concentration of IGF-I (+/- S.E.M.) was 68.6 +/- 8 ng per milliliter in pygmies, as compared with 193 +/- 10 ng per milliliter in controls (P less than 0.001) and 24 +/- 4 ng per milliliter in patients with growth hormone deficiency (P less than 0.05). Mean serum concentrations of IGF-II in controls, pygmies, and growth hormone-deficient patients were 647 +/- 22, 503 +/- 37, and 252 +/- 29 ng per milliliter, respectively. The serum IGF-I concentration was within the normal range in only one pygmy, whereas IGF-II values were within the normal range in 10 of 11. Pygmies appear to have a major defect in the production of IGF-I.
Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes
Authors: Karl-Ludwig Laugwitz, Martin Ungerer, Torsten Schöneberg, Hans-Jörg Weig, Kai Kronsbein, Alessandra Moretti, Katrin Hoffmann, Melchior Seyfarth, Günter Schultz, Albert Schömig
Journal: Circulation (1999)

Background —In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C β-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure. Methods and Results —A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation. Conclusions —Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized β-adrenergic receptor signaling.
Stanley Cobb: A Builder of the Modern Neurosciences
Authors: Frankreem Freemon
Journal: JAMA (1985)

Who was Stanley Cobb? He made no important scientific discoveries, no new clinical observations. But Benjamin V. White, a gastroenterologist who was one of Cobb's students, has written an excellent biography of this teacher and administrator, whose life is interesting and instructive. He began as an ornithologist, became a leading neurologist and neuropathologist,ed in midcarmidcareerpsychiatry psychoanalysis, and ended life as a comparative anatomist and proponent of environmental conservation. Born in Boston in 1887 of an old New England family, Stanley Cobb early in life developed an interest in nature. During vacations from Harvardlege and Medical School, he traveled to many locations throughout North America; his observations of bird life were published in ornithological journals. After graduation from medical school he set out on a carefully designed program of trainingat included one year of neurosurgery with Harvey Cushing, years of neuropsychiatry under Adolph Meyer, and two years traveling Europe, where he
Dapsone-induced haemolytic anaemia
Authors: G. MANFREDI, G. Panfilis, M. ZAMPETTI, F. ALLEGRA
Journal: British Journal of Dermatology (1980)

Journal Article Dapsone‐induced haemolytic anaemia Get access G. MANFREDI, G. MANFREDI Istituto di Clinica Dermosifilopatica, Università di Parma, I‐43100 Parma, Italy Search for other works by this author on: Oxford Academic Google Scholar G. DE Panfilis, G. DE Panfilis Istituto di Clinica Dermosifilopatica, Università di Parma, I‐43100 Parma, Italy Search for other works by this author on: Oxford Academic Google Scholar M. ZAMPETTI, M. ZAMPETTI Istituto di Clinica Dermosifilopatica, Università di Parma, I‐43100 Parma, Italy Search for other works by this author on: Oxford Academic Google Scholar F. ALLEGRA F. ALLEGRA Istituto di Clinica Dermosifilopatica, Università di Parma, I‐43100 Parma, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 3, 1 March 1980, Page 365, https://doi.org/10.1111/j.1365-2133.1980.tb08158.x Published: 01 March 1980
Detection of Superior Sagittal Sinus Thrombosis on FDG PET
Authors: Archi Agrawal, Ramesh Agrawal, Ramesh Asopa, Nawab S. Baghel
Journal: Clinical Nuclear Medicine (2009)

A 51-year-old woman with infiltrating ductal carcinoma of left breast, who postsurgery, chemotherapy, and external radiotherapy presented with recurrence in the right chest wall a year after completion of treatment. An excision biopsy of the right chest wall nodule showed deposits of infiltrating ductal carcinoma. She also complained of excruciating headache. A FDG PET scan was done an hour after intravenous administration of 444 MBq (12 mCi) of F-18 FDG, on a dedicated PET scanner. The scan showed multiple hypermetabolic sites in the mediastinum, liver, spleen, abdomen, right scapula, and right ilium. In addition to all this, a triangular area of uptake was seen along the falx in the region of the superior sagittal sinus. A CT scan confirmed a superior sagittal sinus thrombosis. On contrast-enhanced CT scan an "empty delta sign" was observed in the superior sagittal sinus from enhancement of the dural leaves surrounding the comparatively less dense thrombosed sinus. This sign is highly diagnostic for sagittal sinus thrombosis.
Intracellular Microenvironment‐Responsive Label‐Free Autofluorescent Nanogels for Traceable Gene Delivery
Authors: Bingyang Shi, Hu Zhang, Shi Zhang Qiao, Jingxiu Bi, Sheng Dai
Journal: Advanced Healthcare Materials (2014)

Gene therapy presents a unique opportunity for the treatment of genetic diseases, but the lack of multifunctional delivery systems has hindered its clinical applications. Here, a new delivery vector, autofluorescent polyethyleneimine (PEI) nanogels, for highly efficient and traceable gene delivery is developed. Different from commercial high‐molecular‐weight PEI, the cationic nanogels are noncytotoxic and able to be fragmented due to their unique intracellular microenvironment‐responsive structures. The biodegradable nanogels can effectively load plasmid DNA (pDNA), and the self‐assembled polyplexes can be cleaved after cellular uptake to improve gene transfection efficiency. Most importantly, the nanogels and the nanogel/pDNA polyplexes are autofluorescent. The fluorescence is stable in blood plasma and responsive to the intracellular microenvironment. The breakup of the nanogels or polyplexes leads to the loss of fluorescence, and thus the gene delivery and carrier biodegradation processes can be monitored. The reported multifunctional system demonstrates excellent biocompatibility, high transfection efficiency, responsive biodegradability, controlled gene release, label‐free and simultaneous fluorescence tracking, which will provide a new platform for future scientific investigation and practical implications in gene therapy.
Removal of the Indwelling Catheter
Authors: R. G. Bunge
Journal: JAMA (1966)

To the Editor:—  With respect to Dr. Kelley's method ( 196 :599, 1966) for deflating the retention balloon of a urethral catheter, we have employed a similar procedure for the past 20 years. We have used 2 cc of chloroform, and to prevent any discomfort the bladder is distended with water prior to the injection.
Netherlands is told to get tough on smokers as cancer mortality stagnates
Authors: T. Sheldon
Journal: BMJ (2010)

<h3>BACKGROUND AND PURPOSE:</h3> Rescue endovascular and pharmacologic approaches are increasingly being adopted after recanalization failure of acute large-vessel occlusion strokes with mechanical thrombectomy, with encouraging results. The safety and efficacy of glycoprotein IIb/IIIa inhibitors in ischemic stroke have been investigated, though cangrelor, a recent intravenous P2Y12-receptor inhibitor with a rapid onset/offset of action and a short half-life, may be a valuable option. We compared the safety and efficacy of cangrelor with those of glycoprotein IIb/IIIa inhibitors for refractory occlusions. <h3>MATERIALS AND METHODS:</h3> We performed a retrospective analysis of the ongoing prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke Registry in France between May 2012 and February 2020. Refractory intracranial occlusions of the anterior and posterior circulation were included and defined as recanalization failure of large-vessel occlusion stroke, perioperative target artery reocclusion, or high risk of early reocclusion related to an arterial wall lesion. The primary end point was a favorable outcome, defined as a 90-day mRS of 0–2. Secondary end points were reperfusion, intracranial hemorrhage, and procedural complications. <h3>RESULTS:</h3> Among 69 patients, 15 were treated with cangrelor, and 54, with glycoprotein IIb/IIIa inhibitors. The favorable outcome (adjusted OR = 2.22; 95% CI, 0.42–11.75; <i>P</i> = .348) and mortality (adjusted OR = 0.44; 95% CI, 0.06–3.16; <i>P</i> = .411) rates were similar in both groups. There was no difference in the rates of any intracranial hemorrhage (adjusted OR = 0.40; 95% CI, 0.08–2.09; <i>P</i> = .280), symptomatic intracranial hemorrhage (6.7% versus 0.0%, <i>P</i> = .058), or procedural complications (6.7% versus 20.4%, <i>P</i> = .215). Reperfusion rates were higher in the cangrelor group, though the difference did not reach statistical significance (93.3% versus 75.0% for modified TICI 2b–3; adjusted OR =10.88; 95% CI, 0.96–123.84; <i>P</i> = .054). <h3>CONCLUSIONS:</h3> Cangrelor seems to be as safe as glycoprotein IIb/IIIa inhibitors for managing refractory intracranial occlusion and leads to satisfactory brain reperfusion. Cangrelor is a promising agent in this setting, and additional studies are warranted to confirm our findings.
Effect of Cytosine Arabinoside on Disseminated Herpes Zoster and Vesicle Fluid Interferon.
Authors: David A. Stevens
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Effect of Cytosine Arabinoside on Disseminated Herpes Zoster and Vesicle Fluid Interferon.David A. Stevens, M.D., Thomas F. Waddel, M.D., Thomas C. Merigan, M.D.David A. Stevens, M.D.Search for more papers by this author, Thomas F. Waddel, M.D.Search for more papers by this author, Thomas C. Merigan, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-873_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFifty-three patients with disseminated herpes zoster were studied; 20 of them received intravenous cytosine arabinoside. Experience with an early treatment (first 2 days of dissemination) program suggested cytosine arabinoside shortened dissemination compared with untreated patients seen previously. With increased referral of early disseminated cases, the study population changed to include a greater proportion with milder disease. A double blind study was initiated and is currently in progress. To date, the results (11 patients) in the placebo and cytosine arabinoside groups aren't significantly different. Treatment with cytosine arabinoside shortens dissemination in some patients destined to have prolonged dissemination and visceral complications:... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Stanford, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEffect of cytosine arabinoside on herpes virus infection in renal allograft recipientsChapter 17. Antiviral AgentsAdverse Effect of Cytosine Arabinoside on Disseminated Zoster in a Controlled Trial 1 May 1972Volume 76, Issue 5Page: 873-873KeywordsCytosineInterferonsMetastasisVesicles Issue Published: 1 May 1972 PDF DownloadLoading ...
Importance of maternal history of non-insulin dependent diabetic patients.
Authors: J C Alcolado, R Alcolado
Journal: BMJ (1991)

OBJECTIVE--To assess the family history of diabetes in non-insulin dependent diabetes mellitus with particular emphasis on parental phenotype. DESIGN--Family histories were obtained from an existing computerised database and supplemented by postal questionnaires. SETTING--Diabetic service of a provincial teaching hospital. SUBJECTS--A total of 1326 patients with non-insulin dependent diabetes who had been referred to diabetic clinics over the past 10 years and from whom data had been collected for inclusion in the database, of whom 347 had affected first degree relatives. Nineteen non-white patients were excluded because of the differential hereditability of the disease, and 230 (70%) patients with an affected first degree relative responded to the postal questionnaire. RESULTS--Mothers were implicated in significantly more cases than fathers in patients with a single affected parent: 125 mothers and 48 fathers from database; 82 mothers and 34 fathers from postal questionnaire; p less than 0.001 in both cases. CONCLUSIONS--Maternal influences seem to have an important role in the inheritance of non-insulin dependent diabetes.
Reorganise out of hours rotas
Authors: S. Paterson-Brown
Journal: BMJ (2009)

The editorial by Pounder,1 the article by Purcell Jackson and Tarpley,2 and the Editor’s Choice3 on working time regulations for trainees, particularly surgical trainees, raise several important issues. More flexibility is needed in “interpreting” the average weekly hours worked and craft specialties will require more training …
Health Reform, Research Pave Way for Collaborative Care for Mental Illness
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

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
Social variations in access to hospital care for patients with colorectal, breast, and lung cancer between 1999 and 2006: retrospective analysis of hospital episode statistics
Authors: R. Raine, W. Wong, S. Scholes, C. Ashton, A. Obichere, G. Ambler
Journal: BMJ (2010)

Objectives To determine the extent to which type of hospital admission (emergency compared with elective) and surgical procedure varied by socioeconomic circumstances, age, sex, and year of admission for colorectal, breast, and lung cancer. Design Repeated cross sectional study with data from individual patients, 1 April 1999 to 31 March 2006. Setting Hospital episode statistics (HES) dataset. Participants 564 821 patients aged 50 and over admitted with a diagnosis of colorectal, breast, or lung cancer. Main outcome measures Proportion of patients admitted as emergencies, and the proportion receiving the recommended surgical treatment. Results Patients from deprived areas, older people, and women were more likely to be admitted as emergencies. For example, the adjusted odds ratio for patients with breast cancer in the least compared with most deprived fifth of deprivation was 0.63 (95% confidence interval 0.60 to 0.66) and the adjusted odds ratio for patients with lung cancer aged 80-89 compared with those aged 50-59 was 3.13 (2.93 to 3.34). There were some improvements in disparities between age groups but not for patients living in deprived areas over time. Patients from deprived areas were less likely to receive preferred procedures for rectal, breast, and lung cancer. These findings did not improve with time. For example, 67.4% (3529/5237) of patients in the most deprived fifth of deprivation had anterior resection for rectal cancer compared with 75.5% (4497/5959) of patients in the least deprived fifth (1.34, 1.22 to 1.47). Over half (54.0%, 11 256/20 849) of patients in the most deprived fifth of deprivation had breast conserving surgery compared with 63.7% (18 445/28 960) of patients in the least deprived fifth (1.21, 1.16 to 1.26). Men were less likely than women to undergo anterior resection and lung cancer resection and older people were less likely to receive breast conserving surgery and lung cancer resection. For example, the adjusted odds ratio for lung cancer patients aged 80-89 compared with those aged 50-59 was 0.52 (0.46 to 0.59). Conclusions Despite the implementation of the NHS Cancer Plan, social factors still strongly influence access to and the provision of care.