tbuckley/cabot-search huggingface dataset:
Pain in the back and legs caused by cervical spinal cord compression
Authors: T. W. Langfitt
Journal: JAMA (1967)

Cervical spinal cord compression by tumor or degenerated disk material can cause low back and leg pains which simulate the lumbar disk syndrome. If the patient has roentgenographic evidence of both cervical and lumbar disk disease, the differential diagnosis can be difficult. The pain caused by cord compression tends to be diffuse, involves both legs, and is burning or aching in quality. Lumbosacral nerve root compression produces a sharp, radiating pain in the distribution of the involved root. The results of neurologic examination may be normal at a time when cord compression is sufficient to produce severe pain. The mechanical signs of lumbar disk herniation, limitation in back mobility, and a positive reaction to the straight leg raising test are absent with cord compression.
Abstract P3-04-06: Damage-induced BRCA1 phosphorylation contributes to the timing of end resection
Authors: B Parameswaran, H-C Chiang, Y Lu, Y Hu
Journal: Cancer Research (2013)

Abstract Germline mutations of BRCA1 predispose women to breast and ovarian cancers. BRCA1 functions as a tumor suppressor. A wealth of evidence has established that BRCA1 plays an important role in DNA repair and cell cycle checkpoint control. Efficient repair of double-strand-breaks (DSBs) by BRCA1 is essential to its tumor suppression function. DSBs can be repaired either by homologous recombination (HR) or by nonhomologous end-joining (NHEJ). BRCA1 is hyperphosphorylated upon DSBs. Although phosphorylation of BRCA1 is among the earliest events documented upon DNA damage, the role of BRCA1 phosphorylation in DNA repair remains unclear after more than a decade. It has been proposed that BRCA1 serves as a scaffolding protein that recruits multiple repair proteins to the break sites. One of the BRCA1-containing complexes, MRN (Mre11-Rad50-Nbs1)-BRCA1-CtIP, promotes HR repair by initiating DNA end-resection, the first step in the HR pathway. Mre11 possesses intrinsic nuclease activity, which likely facilitates initial processing of DNA ends for subsequent extensive end-resection. Believed to stimulate the nuclease activity of the MRN complex, CtIP is recruited to the complex by BRCA1. In spite of these useful molecular models, the precise function of BRCA1 in DSB repair, especially the role of its phosphorylation, remains elusive. BRCA1 is phosphorylated by Chk2 kinase upon g-irradiation at serine 988 (human) or serine 971 (mouse). Our data shows that a point mutation in mouse BRCA1 (S971A) that abolishes the Chk2 phosphorylation site impairs end-resection after DSBs. The S971A mutation does not appear to affect the assembly of MRN and CtIP at DSBs, but specifically delays dispersion of BRCA1 from DSBs. Interestingly, BRCA1 is ubiquitinated and degraded by SCFSkp2, and loss of Chk2 phosphorylation at S988 of human BRCA1 impairs its ubiquitination. Previous work has revealed BRCA1 as a scaffold protein for the assembly of HR proteins at DSBs. Paradoxically, BRCA1 also inhibits Mre11 nuclease activity. Our study suggests that BRCA1 plays a dual role in HR. Although BRCA1 is required for initial assembly of the MRN-BRCA1-CtIP complex at DSBs, the exit of BRCA1 from the MRN-BRCA1-CtIP complex is required to relieve its inhibitory effect on Mre11 nuclease activity. Mechanistically, this critical “exit” of BRCA1 from the MRN-BRCA1-CtIP complex is regulated through phosphorylation catalyzed by Chk2 and then degraded by SCFSkp2, which is expressed at S/G2 phases, thus ensuring the initiation of end resection/HR to S/G2 phases of the cell cycle. Our study explains two seemingly paradoxical observations: BRCA1 is required for assembly of the MRN-BRCA1-CtIP complex, but it inhibits Mre11 nuclease activity required for end-resection. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-04-06.
Abstract 1333: Isolation, characterization and expansion of circulating tumor cells in solid cancers
Authors: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean-Paul Thiery, Ken O'Byrne, Chamindie Punyadeera
Journal: Cancer Research (2019)

Abstract Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=300) and lung cancer (n=80) patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence internal [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggests that PD-L1 is frequently expressed on CTCs in HNC and lung cancer and an immunoscore may be able to identify patients likely to benefit from immunotherapy-a current unmet clinical need. Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular diversity present within the tumor, understanding of the disease progression and testing of therapies. Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean-Paul Thiery, Ken O'Byrne, Chamindie Punyadeera. Isolation, characterization and expansion of circulating tumor cells in solid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1333.
Current Comment
Journal: JAMA (1934)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
A Clinical Lecture on Recent Advances in Abdominal Surgery
Authors: C. G. Wheelhouse
Journal: BMJ (1885)

anjtit't!meaptntheardc8F411=41 o ' terti aseptic I inean -i `condition of wbund and dresshi e laute free frbm these changes, -whetherdor rot micrococci be fdund in the outer portion of thb'dresings, fotloese'ba bi.refidered i4iocU6ds'b the application of 'antiseptics supetficially.-lbelieve that lI am righ in asserting that !the 9pinion of &r rtbat ms jority df surgene at The present time is, that the safeg 'Gitrara 'aba t b~ood-poj §onlnk tiay b mun h increased by the local tLie-of a4ntiseptics,and th4t th i on of! the hour is what-is the 'beit, !i'w.pofiil, it ii+itati$n'a;d most convenient and econoriical aitid4tidIfot -#e iftlset number have been tried, ari4 mAh t or-other of the §e requirem6Ats., J7M*L4ifYti-e.t s !is sitiVo cer- t4tity that they aid the vitaI ilaibitory foree, O tg he0tiVJgonistic ageicks vridh *hld 'a1no* eve hse.After thei ubHeOato?~etliire'iork exJthe d,a of' phendi 4id in 1863, this"sb talce was eiilfb3Yd 'by' many suteon(ithe' lqMj a CalkEnder ambng'then.)I f o,aidb Sir`3osoph Thster as crbhollSed putty,;i r C4e6 6f rio brd fraturb.Aithriu this sIbtstmide rfulfiedthe 'rit A ofcheapnets apd.6te usefuilness, its AbSolutep icrobictd 'afid atitlseptic :OWer, is c^hrk; tively small, namely,"' 1 in 81! (Miqtiit).'It k i''sbdri 'o.d teribe irtitating to tb'6tid apt toPrduc llc'pd3sbii.gAl- tl6ugh:the`latit JdilA-of% 11:44d $II&i sa t hsido, t bListe'r (1 inA20 t6 -1 ii 40)!,pa1iefits vary s6lvery'MnIii's6ceptIBility that both they atid their 'Oufge6w oftenJ 'ep6e6d; 'the penalty d exceeding the limilta It* 4ulati ¶ity, while rendering' it iore,htci6ntin the deeper recesses and sinusep of a wound, caused it to losS Dood deal of its efficacy suiperfidally, yhy its.waint of persistence 'and,st#lng power.This was partly, but naot 6utirely, overcome by, Listerl' gafi wbich, again, was expensive arid unicertain , Chloride of zinc, in the form of Burnett's fluid; had beSn 'ued"l6ng before this at the l!iiddleseX Hospital by the late Mr. Doe N ¶qrg6A to destroy cancer-germs in wounds; and it was found, wlhei apMiied strong, in a saturated solution, to be a good afitiseptid.Its' m-iro- bicide power, ho6tver, is'iio* sat 'a.nair oItaer-ih;1Aatatee namely, 1 in 62.In combinatii'with snution of 'cabtolic '*cd, dl with many othera, found, and still find-it a valbablo app}iction to
Lymphogranuloma venereum
Authors: A. J. Abrams
Journal: JAMA (1968)

The incidence of lymphogranuloma venereum in the United States is increasing. A large segment of this increase is due to dissemination of the disease by American soldiers returning from Southeast Asia. Seventeen of 20 patients seen at a large military hospital had the triad of typical inguinal or femoral adenopathy, positive Frei test, and significant complement fixing antibodies; however, no correlation was found between the clinical severity of the disease and quantitation of the test results. A 21-day course of either tetracyclines or sulfonamides was equally effective in eradicating the disease in all but one case. Aspiration of fluctuant nodes to prevent rupture proved an effective therapeutic adjunct.
Heroin-associated nephropathy. A nationwide problem
Authors: E. E. Cunningham
Journal: JAMA (1983)

Heroin-associated nephropathy (HAN) is a common cause of end-stage renal disease (ESRD) among 18- to 45-year-old patients in the Buffalo area. To assess the importance of HAN nationwide, a questionnaire was sent to 130 dialysis units or sections of nephrology throughout the United States. Fourteen metropolitan areas represented by 23 respondents reported 98 cases of HAN. Ninety-two patients (93.9%) were black. Black men made up the single largest group, with 77 patients (78.6%). The ESRD had already developed in 66 (67.3%) of the patients with HAN. The occurrence of HAN was high in those units that responded to the questionnaire. These figures, however, do not represent the prevalence of HAN in the United States. The economic impact of treating HAN may be striking. The estimated cost of maintaining just the 66 addicted patients with renal failure on dialysis would be greater than $1 million yearly. (<i>JAMA</i>1983;250:2935-2936)
Rationing Failure
Authors: Peter A. Ubel
Journal: JAMA (1993)

Because of a shortage of transplantable livers and hearts, the transplant community has had to decide—by who gets an organ—who lives or dies. Despite this shortage, whether one has previously received a transplant is not used as a criterion to distribute organs. The existing allocation system distributes 10% to 20% of available hearts and livers to retransplant patients. This article examines three differences between primary transplantation and retransplantation that may affect the priority that retransplant candidates should receive in vying for organs: (1) the special obligations that transplant teams have not to abandon patients on whom they have already performed a transplant, (2) the fairness of allowing individuals to get multiple transplants while some die awaiting their first, and (3) the difference in efficacy between primary transplantation and retransplantation. Only this last difference holds up to critical analysis. Our moral duty to direct scarce, lifesaving resources to those likely to benefit from them, suggests that, all other things equal, primary transplant candidates should receive priority because their mortality after transplantation is lower. Consistency also demands that previous transplant history be taken into account, as we already allocate organs according to ABO blood group matching, a factor that affects transplant outcome approximately the same amount as a previous transplantation. We therefore conclude that the system should be revised so that primary transplant candidates have a better chance of receiving organs than retransplant candidates. (<i>JAMA</i>. 1993;270:2469-2474)
Cardiovascular Physiology
Journal: JAMA (2002)

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
Systemic and Coronary Hemodynamic Effects of Isosorbide Dinitrate
Journal: JAMA (1963)

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
Evidence From Randomized Controlled Trials, Meta-analyses, and Subgroup Analyses
Authors: Mark J. Bolland
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
La radiothérapie pénétrante.
Journal: JAMA (1930)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
ST03: A randomized trial of perioperative epirubicin, cisplatin plus capecitabine (ECX) with or without bevacizumab (B) in patients (pts) with operable gastric, esophagogastric junction (OGJ), or lower esophageal adenocarcinoma.
Authors: Elizabeth Catherine Smyth, Ruth E. Langley, Sally P. Stenning, Laura Stevenson, Claire Robb, William H. Allum, Heike Grabsch, Derek Alderson, Angela M. Riddell, Thomas Crosby, Robert Mason, Michael Griffin, Wasat Mansoor, Fareeda Y. Coxon, Stephen Falk, Debra Furniss, Gary William Middleton, Katherine Anne Sumpter, Jane M. Blazeby, David Cunningham
Journal: Journal of Clinical Oncology (2013)

TPS4156 Background: Perioperative ECX chemotherapy is a standard of care for localised operable gastric/OGJ/lower oesophageal adenocarcinoma (Cunningham, NEJM 2006). In combination with chemotherapy B, a monoclonal antibody targeting VEGF-A, results in improved response rates (RR) and progression free survival in advanced gastric cancer (Ohtsu, JCO 2011). ST03 aims to assess the safety and feasibility (stage I, 200 pts) and efficacy (stage II) of the addition of B to perioperative ECX chemotherapy. Methods: ST03 is a multicentre, open-label, phase II/III randomised trial open at 106 UK centres. Eligibility criteria are histologically proven, untreated, resectable, lower oesophageal, OGJ or gastric adenocarcinoma; age ≥18 years; WHO PS 0-1; and adequate cardiac ejection fraction (EF). Exclusion criteria are TIA/CVA or MI ≤1 year; uncontrolled hypertension; ≥ Grade 2 NYHA heart failure; recent gastrointestinal inflammatory conditions or major surgery/trauma/open biopsy &lt;28d of study entry. Pts receive 3 pre- and 3 postoperative ECX (epirubicin 50 mg/m2 iv D1, cisplatin 60 mg/m2 iv D1 and capecitabine 1250mg/m2/D1-21) +/- B 7.5mg/kg D1 q3wk during chemotherapy, then 6 B q3wk (investigational arm). Surgery is pre-specified and laparoscopic procedures allowed only after quality assurance review. All specimens undergo central pathology review; blood and tissue collection for translational studies is ongoing. Stage I Safety results including cardiac EF have been reported (Okines Ann Oncol 2012). The stage II primary outcome measure is overall survival. Secondary outcome measures are RR, resection rate, disease free survival, toxicity, and QoL. MRI and PET substudies are ongoing. 877 of 1,100 pts have been recruited, accrual expected to complete in Q4 2013. A pilot study within ST03 randomising HER2 positive pts to ECX ± lapatanib (L) opened Q1 2013 and will assess safety, HER2 positivity rate and feasibility in 40 pts randomised between standard ECX and modified ECX+L. Trial sponsored and co-ordinated by the MRC Clinical Trials Unit and funded by Cancer Research UK (CRUK06/025, NCT00450203). Clinical trial information: NCT00450203.
Tests of testicular function
Authors: R. L. Landau
Journal: JAMA (1969)

The evaluation of testicular function can be readily divided into two categories, those procedures designed to evaluate fertility and those restricted to the testing of the endocrine function of the glands. The term "hypogonadism" generally refers to the condition resulting from a deficiency of male hormone. Often hypogonadism includes or is accompanied by seminiferous-tubule failure or impairment. However, there are exceptions in which spermatogenesis appears intact despite a clinically apparent androgen deficiency. Except for functioning carcinoma of the interstitial cells of Leydig, no syndrome characterized by testicular androgen excess has been described. <h3>Endocrine Function</h3> Interest in the internal secretion of the testis was a dominant factor influencing some of the fathers of endocrinology.<sup>1</sup>The effects of castration and prepubertal testicular failure have been well-described. The physical findings of the androgen-deficient adult male must be included among the tests for testicular androgen secretion, for they remain the hallmark by which