tbuckley/cabot-search huggingface dataset:
Correction/Clarification about FDA Review Documents
Authors: Erick Turner
Journal: PLoS Medicine (2005)

Essay [1] about how the Food and Drug Administration’s (FDA’s) review of documents can serve as a source of clinical trials data, but she follows it up with the statement, “However, it is difﬁ cult to have conﬁ dence in data released by sponsors when the data have not been subjected to external, independent peer review. Furthermore, this information is not integrated with other data, or indexed” [2].While I agree with the second assertion, the ﬁ rst assertion—that the data are not subjected to external, independent peer review—is off the mark. FDA reviews are indeed external and independent to the sponsor. These reviews are conducted not by the sponsors but by physicians and scientists employed by the United States government. True, the data originate with the sponsor. However, once the sponsor submits data to the FDA, a level of rigor and scrutiny is applied to them that is arguably higher than what occurs in the typical journal manuscript review process. First, FDA reviewers typically revisit the original protocol submitted before the study was conducted in order to verify that the sponsor has not engaged in hypothesizing after the results are known (“HARKing”) [3]. By contrast, journal reviewers typically do not have access to the original protocol. As a result, they must trust that HARKing has not occurred, a dubious assumption in view of recent data [4]. Second, FDA statistical reviewers obtain the raw data from the sponsor, and determine whether the sponsor’s ﬁ ndings can be replicated. By contrast, journal reviewers typically have access to only the summary statistics reported (perhaps selectively) to them by the authors or the sponsors. Consequently, reviewers can only speculate whether they could replicate the ﬁ ndings. As a result, I believe that the FDA review process warrants a higher level of conﬁ dence than the conventional journal manuscript review process. Erick Turner
Beta-Receptor Activity in Aorta
Authors: JEROME H. FLEISCH, HARRIET M. MOLING, BERNARD B. BRODIE
Journal: Circulation Research (1970)

Helically cut thoracic aortic strips (from rats, rabbits, and guinea pigs) in a state of low to moderate tone and under the influence of alpha-receptor blockade relaxed in response to isoproterenol. Propranolol blocked these relaxations. Helically cut thoracic aortic strips from cats and abdominal aortic strips from rats, rabbits, and cats were not relaxed by isoproterenol. In addition, aortic beta-receptor activity of rats and rabbits decreased with increasing age. The ability of thoracic aortas to be relaxed by isoproterenol was lost when rats were 90 days old and when rabbits were 2 years old. Significant loss of beta-receptor activity was not evident in rat trachea and stomach. Sodium nitrite completely relaxed thoracic and abdominal aortas from all species including thoracic aortas from old rats and rabbits. We conclude: (1) there are species differences in the response of thoracic aortic strips to beta-receptor stimulation; (2) a gradient in beta-receptor activity exists in the aorta with greater activity in the thoracic aorta and a relatively small amount of activity in the abdominal aorta; and (3) aortic beta-receptor activity decreases with increasing age.
31P Magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure
Authors: W. Aufferman, S. T Wu, N. Derugin, W. Parmley, C. Higgins, V. Kapelko, J. Wikman-Coffelt
Journal: Cardiovascular Research (1990)

Journal Article 31P Magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure Get access Wolfgang Aufferman, Wolfgang Aufferman Search for other works by this author on: Oxford Academic PubMed Google Scholar Shao T Wu, Shao T Wu Search for other works by this author on: Oxford Academic PubMed Google Scholar Nikita Derugin, Nikita Derugin Search for other works by this author on: Oxford Academic PubMed Google Scholar William Parmley, William Parmley Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles Higgins, Charles Higgins Search for other works by this author on: Oxford Academic PubMed Google Scholar Valeri Kapelko, Valeri Kapelko Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan Wikman-Coffelt Joan Wikman-Coffelt Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 1, January 1990, Pages 57–64, https://doi.org/10.1093/cvr/24.1.57 Published: 01 January 1990 Article history Received: 17 August 1988 Accepted: 25 July 1989 Published: 01 January 1990
Managing Financial Conflict of Interest in Biomedical Research
Authors: Sally J. Rockey
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
IT-09 * PHASE I STUDY OF SAFETY, TOLERABILITY AND IMMUNOLOGIC EFFECTS OF A SURVIVIN PEPTIDE MIMIC VACCINE (SurVaxM) IN PATIENTS WITH RECURRENT MALIGNANT GLIOMA
Authors: R. Fenstermaker, L. Mechtler, J. Qiu, K. Mogensen, M. Ahluwalia, A. Adjei, K. Lee, M. Ciesielski
Journal: Neuro-Oncology (2014)

BACKGROUND: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in malignant gliomas and other cancers. Induction of cytotoxic immunity against survivin is an attractive antitumor strategy. Preclinical studies demonstrated the ability of a KLH-conjugated survivin peptide mimic (SVN53-67/M57-KLH; SurVaxM) to induce an immune response capable of inhibiting the growth of gliomas in mice, and killing human glioma cells ex vivo. The vaccine is predicted to be immunogenic in humans with HLA-A*02, HLA-A*03, HLA-A*24 and other haplotypes and pre-clinical studies demonstrate potent and specific cytokine-supported antitumor CTL responses. METHODS: Nine patients with survivin-positive, recurrent malignant gliomas and either HLA-A*02 or HLA-A*03 haplotypes received a series of 4 subcutaneous injections of SurVaxM at 2 week intervals. MRIs were performed at baseline, week 8, and at subsequent intervals. RESULTS: SurVaxM was well tolerated with no SAE, and mostly grade one AE. 6 of 9 patients experienced grade 1 localized erythema at the injection site, likely related to the vaccine. 3 patients reported grades 1 or 2 fatigue, 2/9 experienced myalgia, possibly related to the study drug. Grade 1 lymphopenia was seen in 3/9 patients and grade 1 or 2 leukopenia was recorded in 3 patients. The only grade 3 AE, a seizure, was not related to the vaccine. The majority of patients developed specific cellular and humoral immune responses to survivin and 3 of 8 patients (all with GBM), who are evaluable for clinical response, have stable disease after more than 12 months of follow-up. All others have had progressive disease. Survival data will be described. CONCLUSION: This study demonstrated the safety and tolerability of SurVaxM in patients with recurrent or progressive malignant glioma following failure of standard therapy. SurVaxM proved to be immunogenic in most patients. A phase II clinical trial of SurVaxM is planned.
Licorice-induced pseudoaldosteronism. Hypertension, hypokalemia, aldosteronopenia, and suppressed plasma renin activity
Authors: J. W. Conn
Journal: JAMA (1968)

Hypertension, initially ncrmokalemic, was eventually associated with hypokalemia, alkalosis, suppressed plasma renin activity, and aldosteronopenia in a 58-year-old man who had ingested two to three 36-gm licorice candy bars daily for six years to seven years. Metabolic balance studies recorded complete recovery upon cessation of licorice ingestion. The syndrome was reproduced experimentally by oral administration of ammonium glycyrrhizate, the compound in licorice responsible for sodium retention. In categorizing mechanisms of hypertension, it is important to assess the functional state of the renin-aldosterone system by measuring both factors. When both yield low values it is likely that a potent sodium-retaining substance, other than aldosterone, either of endogenous or of exogenous origin, is at work. Licorice-induced hypertension serves a model of hypertensive disease developing as the result of ingestion of a foodstuff possessing sodium retaining activity.
Simulation in surgical training
Authors: D A S Pearce
Journal: BMJ (1990)

Acute otitis media SIR,-Mr George G Browning and colleagues state that diagnosing acute otitis media is not easy even when carried out by specialists.'Unfortunately, in two of the studies quoted2 the diagnosis was made predominantly by doctors without specialist training.If only half of children with otalgia have acute otitis media some ofthe figures quoted may be underestimated by a factor of two.Even if the data are accurate, surely a failure of resolution in 15% of "untreated" children is unacceptably high?The advocated policy of withholding antibiotics
Change in Aortic End-Systolic Pressure by Alterations in Loading Sequence and Its Relation to Left Ventricular Isovolumic Relaxation
Authors: Fujimasa Kohno, Toshiaki Kumada, Masashi Kambayashi, Wataru Hayashida, Noboru Ishikawa, Shigetake Sasayama
Journal: Circulation (1996)

Background A brief, sustained constriction of the descending and the ascending aortas produces systolic loads at different times during ejection, and descending intervention prolongs left ventricular (LV) relaxation more than ascending intervention. Although alterations in the sequence of loading the ventricle have been suggested as a cause of such load-induced relaxation abnormalities, the relation of the loading system to relaxation has been unclear. Methods and Results LV peak systolic pressure was elevated by approximately 40 mm Hg by constricting the descending and ascending aortas in seven anesthetized dogs. The descending intervention increased aortic end-systolic pressure (AoESP, 110.4±9.3 to 150.8±11.5 mm Hg; P &lt;.05), reduced aortic flow ( P &lt;.05), and prolonged LV relaxation (time constant [T], 31.9±4.4 to 69.8±12.8 ms; P &lt;.05). LV ejection time was reduced, but the systolic time interval was unchanged. In contrast, ascending intervention decreased AoESP (111.9±11.4 to 101.5±10.3 mm Hg; P &lt;.05), reduced aortic flow ( P &lt;.05), and prolonged T (31.2±5.4 to 42.2±8.3 ms; P &lt;.05), whereas ejection time and systolic time interval increased (both P &lt;.01). Prolongation of T was significantly greater during descending intervention ( P &lt;.05) and was associated with an increase in AoESP during descending intervention but a decrease in AoESP during ascending intervention. Conclusions Descending intervention induced greater prolongation of T than ascending intervention. Prolongation of T was closely related to an increase in AoESP in the descending intervention but a decrease in AoESP in the ascending intervention. These data suggest that not only the loading sequence but also the pressure level at the onset of isovolumic relaxation determines LV relaxation.
Tc-99m Sestamibi Uptake by Cerebellar Metastasis From Bronchogenic Carcinoma
Authors: WEI-JEN SHIH, K KADZIELAWA, CHARLES LEE, EDWARD B. MOODY, U YUN RYO
Journal: Clinical Nuclear Medicine (1993)

Tc-99m sestamibi has been used to detect primary brain and lung tumors. The authors report a patient who underwent brain imaging to differentiate tumor from abscess in the cerebellum because of a ring-like enhancement lesion on a brain CT scan. An abnormal area of increased sestamibi uptake in the right cerebellum was demonstrated planar and on a SPECT imaging. The removed tumor was confirmed to be poorly differentiated metastatic carcinoma.
Chromoendoscopic findings useful for diagnosis and assessment of treatments for ileac lesions of Henoch–Schönlein purpura
Authors: S. Oomori, K. Abe, S. Takagi
Journal: Endoscopy (2009)

Henoch–Schönlein purpura (HSP) is a systemic disease characterized by the deposition of immune complexes and involving multiple organs [1]. One of the organs commonly affected is the gastrointestinal tract. Since approximately 15 % of patients with HSP develop purpura after the appearance of digestive symptoms [2], early diagnosis by detection of gastrointestinal lesions using endoscopy and immediate treatment are necessary. Here, we report two cases of HSP examined by chromoendoscopy with indigo carmine contrast. This procedure clearly delineates the endoscopic features of active ileac lesions of HSP, and has also been proven as useful for treatment assessment.
Diagnosis of Growth Hormone Deficiency and the Treatment of Short Stature
Authors: Deborah Rotenstein
Journal: JAMA (1989)

To the Editor.—  I read with interest the Special Communication by Lantos et al 1 regarding ethical issues in growth hormone therapy. Several concerns came to mind. The comment that there is widespread agreement about the criteria for diagnosing  growth hormone  may not be true. A majority (60% to 80%) of children with growth hormone deficiency, as defined in the  sense, will have increased levels of circulating growth hormone after injection of growth hormone releasing factor. 2 This observation makes the term classic growth hormone  an inexact label. The authors suggest that growth hormone treatment is ethical for those who have classically defined growth hormone deficiency. When the diagnosis of growth hormone deficiency depends on the choice of stimulus or secretagogue, ethical considerations concerning who is a candidate for treatment become even more complex.  In terms of cosmetic therapy, the authors state that for most pediatricians,
Prisoners' treatment is "bordering on torture," charity says
Authors: O. Dyer
Journal: BMJ (2002)

The International Committee of the Red Cross is to establish a permanent presence in the prison camp at Guantanamo Bay naval base in Cuba, after pictures released by the US navy caused an international outcry at what appeared to be degrading treatment of the al-Quaida and Taliban prisoners from Afghanistan who are held there.

A four member Red Cross team, including a doctor, reviewed conditions at the camp and visited prisoners individually. Their report will not be made public but will be presented to US authorities.

A Red Cross spokesman told the media, however, that the United States had contravened the …
Additional Data on the Shooting of President Kennedy
Authors: John K. Lattimer
Journal: JAMA (1993)

The journalhas performed a great service in persuading Humes, Boswell, and Finck to answer extended queries about the details of the autopsy of President Kennedy.<sup>1,2</sup>They replied directly to many of the questions raised by the critics of the Warren Commission report, an excellent move toward "full disclosure." However, we must remember that Humes, Boswell, and Finck wrote their autopsy report without seeing the color photographs or studying in detail the roentgenograms of the body that were taken at the autopsy. The photographs had been confiscated by the Attorney General (the President's brother) without being developed, and they were then turned over to the National Archives (from which they have never been released). The basis for this confiscation was the family's desire that the photographs of the President's exploded head not appear in every bookstore window, as they would have had See also pp 1507, 1540, and 1552.
Treatment of acquired junctional melanocytic naevi by Q-switched and normal mode ruby laser
Authors: W. Westerhof, M. Gamei
Journal: British Journal of Dermatology (2003)

Background Acquired junctional melanocytic naevi are harmless pigmented lesions of the epidermis, which can be of cosmetic concern. Various therapeutic approaches have been used in the treatment, but all these methods produce postoperative scarring or alterations in skin texture. Pigment laser treatment of benign pigmented lesions has shown a low potential for scarring by selectively targeting melanosomes in melanocytes and keratinocytes. Objective To find a fast, effective and safe treatment for the removal of acquired junctional melanocytic naevi. Patients/Methods We first studied the effect of the Q-switched and normal mode ruby laser on 12 patients (eight women and four men) with acquired melanocytic naevi. The effect was monitored by histology and clinical photography. Results If the response to one treatment with the Q-switched laser mode was not completely effective, the lesions were subsequently treated with one or two sessions with the laser in normal mode. All flat lesions responded completely. After a follow-up period of 1 year they had not recurred. Slightly elevated lesions showed only a partial response, e.g. disappearance of the junctional part of the naevus but recurrence of the dermal part of the naevus. Red–brown junctional naevi as seen in skin types I and II did not respond well to ruby laser treatment. Conclusions The Q-switched ruby laser was very successful in completely removing flat (non-palpable) acquired junctional melanocytic naevi, but not compound naevi, with one to three treatment sessions, without any scarring or pigmentary disturbance.
Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.
Authors: P Collin, E Pukkala, T Reunala
Journal: Gut (1996)

BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin9s lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin9s lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.
HEMATURIA: ITS INTERPRETATION
Authors: DANIEL N. EISENDRATH
Journal: JAMA (1926)

In the past, we have usually associated the term hematuria with the variety in which the urine was visibly blood-tinged or contained clots. With the rapid increase of the number of life insurance and periodic health examinations, the significance of even microscopic hematuria has assumed a different aspect. For years, urologists have emphasized the importance of a thorough examination in every case of macroscopic hematuria; and although this cannot be too strongly urged today, the possibility of recognizing a bleeding nephritis, a ureteral stricture and other symptoms has made it vital to regard even the microscopic presence of blood in the urine as worthy of a painstaking search for its seat.  During the last decade, much light has been thrown on some hitherto obscure causes of hematuria, and my special object in this paper is to review these contributions and to attempt to correlate the various portions of a question
Human Neonatal Fc Receptor Mediates Transport of IgG into Luminal Secretions for Delivery of Antigens to Mucosal Dendritic Cells
Authors: Masaru Yoshida, Steven M Claypool, Jessica S Wagner, Emiko Mizoguchi, Atsushi Mizoguchi, Derry C Roopenian, Wayne I Lencer, Richard S Blumberg
Journal: Immunity (2004)
Clinical Differentiation Between Thyroid Cancer and Benign Goiter
Authors: Katsutaro Shimaoka
Journal: JAMA (1962)

The ability of skilled physicians to estimate cancer risk in nontoxic goiter was determined by reviewing 235 evaluations of patients referred as thyroid cancer suspects and comparing the diagnostic impressions with the subsequent clinical and histological findings. Of 202 patients classified as "benign" on clinical evaluation, 2% proved to have thyroid cancer. In contrast, 28% of those classified as "suspected of cancer" and 53% of those classified as "probably cancer" did indeed have malignant goiters. Furthermore, although only 63 patients with "benign" goiters were subjected to early thyroidectomy, these included all 4 with thyroid cancer so far identified in this group. These figures indicate that patients with goiter can be divided quite successfully into low and high cancer-risk groups and that preoperative selection is justified.
Any changes in prevalence of autism must be determined
Authors: M. F Blaxill
Journal: BMJ (2002)

EDITOR—Because of the current concern over the rising incidence of autism the BMJ owes its readers better information than a letter based on comments by a focus group of interested parties.1 Would the journal have published a letter from a focus group of parents who believed that MMR vaccine (measles, mumps, and rubella vaccine) had caused their child's autism? I doubt it.

Rigorous methods are especially important because of a controversial current hypothesis.2 Fombonne has argued that despite reported …