tbuckley/cabot-search huggingface dataset:
A Technique for Leg Measurements
Authors: W. O. Frick
Journal: JAMA (1965)

To the Editor:—  I was interested in Dr. Edgar L. Ralston's recommendation of scanograms as the definitive way of measuring the length of the lower extremities (questions and answers, JAMA  192 :654 [May 17] 1965). In our office practice of radiology, we have frequently had occasion to measure the length of the lower limbs. We had used the scanographic technique for some time and found it cumbersome and subject to annoying technical errors.  For the past several years we have been using a very simple method. A test tube half filled with some radiopaque liquid is taped to the vertical x-ray table at the level of the middle of the patient's pelvis. The patient then stands barefoot in front of this tube, with legs straight, and a single anteroposterior x-ray film of the pelvis is made. The horizontal fluid level of the liquid records on the film and measurements can
Regulation of key proteins in Alzheimer’s disease molecular pathogenesis by ubiquilin-1
Authors: Mari Takalo, Jayashree Viswanathan, Teemu Natunen, Kaisa MA Kurkinen, Heikki Tanila, Hilkka Soininen, Rudolph E Tanzi, Mikko Hiltunen, Annakaisa Haapasalo
Journal: Molecular Neurodegeneration (2013)

Background Ubiquilin-1 is a ubiquitin-like protein involved in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative disorders via different mechanisms. UBQLN1 UBQ-8i genetic variation associates with increased AD risk. Ubiquilin-1 protein functions as a molecular chaperone controlling amyloid precursor protein (APP) trafficking and processing and presenilin (PS) levels and subcellular targeting. Ubiquilin-1 harbors a ubiquitin-like (UBL) domain interacting with the proteasome and a ubiquitinassociated (UBA) domain binding polyubiquitinated proteins. Thus, it may target polyubiquitinated proteins to degradation. Alternative splicing of UBQLN1 generates four transcript variants (TV) with varying domain structures, suggesting that diverse variants may specifically interact with and regulate different proteins and cellular functions.
Abnormality of a Thiamine-Requiring Enzyme in Patients with Wernicke-Korsakoff Syndrome
Authors: John P. Blass, Gary E. Gibson
Journal: New England Journal of Medicine (1977)

We studied a thiamine-requiring enzyme in cultured cells from four patients with the Wernicke-Korsakoff syndrome to determine whether these patients have a genetic predilection to thiamine deficiency. Transketolase in fibroblasts from the patients with the syndrome bound thiamine pyrophosphate less avidly than control lines. The apparent Km for thiamine pyrophosphate was 195 +/- 31 micron for transketolase in extracts of the patients' cells as compared to 16 +/- 2 micron in six control lines (means +/- S.E.M.: P less than 0.001). The ranges were 146 to 281 micron for the patients and 12 to 20 micron for the controls. The abnormality in transketolase persisted through serial passages in tissue culture in cells grown in medium containing excess thiamine and no ethanol, indicating that the aberrations were genetic rather than dietary. The abnormality of transketolase in this syndrome would presumably be clinically unimportant if the diet was adequate. These patients appear to have deleterious inborn enzymatic abnormalities of a type originally postulated by Garrod.
Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E.
Authors: T Ebara, R Ramakrishnan, G Steiner, N S Shachter
Journal: Journal of Clinical Investigation (1997)

The mechanism of apolipoprotein (apo) CIII-induced hypertriglyceridemia remains uncertain. We crossed apoCIII transgenic and apoE gene knockout (apoE0) mice, and observed severe hypertriglyceridemia with plasma triglyceride levels of 4,521+/-6, 394 mg/dl vs. 423+/-106 mg/dl in apoE0 mice, P < 0.00001 for log(triglycerides [TG]). Cholesterols were 1,181+/-487 mg/dl vs. 658+/-151 mg/dl, P < 0.0001. Lipoprotein fractionation showed a marked increase in triglyceride-enriched chylomicrons+VLDL. This increase was limited to the lowest density (chylomicrons and Sf 100-400) subfractions. Intermediate density lipoproteins (IDL)+LDL increased moderately, and HDL decreased. There was no significant increase in triglyceride production in apoCIII transgenic/apoE0 mice. The clearance of VLDL triglycerides, however, was significantly decreased. Lipoprotein lipase in postheparin plasma was elevated, but activation studies suggested LPL inhibition by both apoCIII transgenic and apoCIII transgenic/apoE0 plasma. ApoCIII overexpression also produced a marked decrease in VLDL glycosaminoglycan binding which was independent of apoE. The predominant mechanism of apoCIII-induced hypertriglyceridemia appears to be decreased lipolysis at the cell surface. The altered lipoprotein profile that was produced also allowed us to address the question of the direct atherogenicity of chylomicrons and large VLDL. Quantitative arteriosclerosis studies showed identical results in both apoCIII transgenic/apoE0 and apoE0 mice, supporting the view that very large triglyceride-enriched particles are not directly atherogenic.
An Unusual Fixation
Authors: Sam Vee
Journal: JAMA (1981)

have a compliment fixation, announced my patient in a matter-of-fact voice, as if this neurosis were a common occurrence.  It is most unusual, I remarked,  have a fixation on a laboratory test. Are you a bacteriologist or a laboratory technician?  Neither. I am a family physician, with a neurosis that has nothing to do with the lab. My hang-up is compliment, not complement.  Please explain.   get tense to a point of panic when someone pays me a compliment, regardless of its nature. My wife and children have learned to avoid praising me or anything I do, but how can I warn friends or strangers?  When did this strange phobia begin?   think I had a vague distrust of praise all my life, but became consciously aware of it at an official banquet when the chairperson introduced me as a brilliant exponent of lusterless ideas.  A strange compliment,
LEPTOSPIROSIS IN CATTLE
Authors: James A. Baker, Ralph B. Little
Journal: The Journal of Experimental Medicine (1948)

From abnormal milk of cows an agent has been transmitted to guinea pigs, rabbits, mice, and embryonated eggs. This agent caused a febrile reaction in guinea pigs and rabbits and an inapparent infection in mice. In early passages embryonated eggs were unaffected but later death of embryos occurred 7 days after inoculation. When blood from infected guinea pigs or chorioallantoic fluid from infected eggs was inoculated subcutaneously or intranasally into young calves, fever with albuminuria and more rarely hemoglobinuria was produced, in lactating cows the infection resembled that seen in animals with natural disease. Pen contact of normal cows and calves with infected calves resulted in inapparent infection. Autopsies showed that in addition to causing altered milk secretion, the agent damaged the kidneys and produced an interstitial nephritis. The agent was recovered from blood and milk during the febrile period and was demonstrated in the urine for periods long afterwards. Antibodies for the spirochete were found in the sera of experimental animals and of cows recovered from the natural disease. The blood of infected guinea pigs, the chorioallantoic fluid from infected eggs, and the blood or urine from experimentally infected calves yielded a culture of a spirochete which appeared identical with the infective agent in comparative tests of physical, pathogenic, and immunological properties.
Points: Urological complications of renal transplantation
Authors: R W Blamey
Journal: BMJ (1982)

September, p 77) express surprise that deaths due to smothering of a baby by a cat do not occur more often.They do not occur more often because most mothers are well aware of the danger.A cat net is a standard piece of baby equipment which is routinely stretched over the pram when it is left unattended in a garden or anywhere frequented by cats.I am astonished that this simple expedient, dictated by common sense rather than by epidemiology, gets no mention in your "Any Questions."'
α- and β-Papillomavirus infection in a young patient with an unclassified primary T-cell immunodeficiency and multiple mucosal and cutaneous lesions
Authors: Manuela M. Landini, Cinzia Borgogna, Alberto Peretti, Enrico Colombo, Elisa Zavattaro, Renzo Boldorini, Umberto Miglio, John Doorbar, Paolo Ravanini, Rajesh Kumar, Daniele Moratto, Raffaele Badolato, Marco De Andrea, Marisa Gariglio
Journal: Journal of the American Academy of Dermatology (2014)
Heberden Oration 1980: aspects of the cell biology of the rheumatoid synovial lesion.
Authors: S.M Krane
Journal: Annals of the Rheumatic Diseases (1981)

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of Transcription Start Sites (TSSs) in several species. Strikingly, ~ 72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probed these unassigned TSSs and showed that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we developed Cap Trap RNA-seq, a technology which combines cap trapping and long reads MinION sequencing. We trained sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveiled the importance of STR surrounding sequences not only to distinguish STR classes, as defined by the repeated DNA motif, one from each other, but also to predict their transcription. Excitingly, our models predicted that genetic variants linked to human diseases affect STR-associated transcription and correspond precisely to the key positions identified by our models to predict transcription. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
Biomarker Analyses in CLEOPATRA: A Phase III, Placebo-Controlled Study of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive, First-Line Metastatic Breast Cancer
Authors: José Baselga, Javier Cortés, Seock-Ah Im, Emma Clark, Graham Ross, Astrid Kiermaier, Sandra M. Swain
Journal: Journal of Clinical Oncology (2014)

Purpose To explore the prognostic and/or predictive value of human epidermal growth factor receptor 2 (HER2) pathway–related biomarkers in the phase III CLEOPATRA study of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer. Patients and Methods Mandatory tumor and serum samples were collected (N = 808; 58% to 99.8% were assessable), and amphiregulin, betacellulin, epidermal growth factor (EGF), transforming growth factor alpha, EGF receptor, HER2, HER3, insulin-like growth factor 1 receptor, PTEN, phosphorylated AKT, PIK3CA, CMYC, serum HER2 extracellular domain (sHER2), and FCγR were assessed using appropriate assays. Two types of correlations were investigated using univariable Cox regression: predictive effects (qualitative association of biomarkers with pertuzumab progression-free survival [PFS] benefit) and prognostic effects independent of treatment arm (relationship of each biomarker to clinical outcome in both arms pooled). Results Pertuzumab consistently showed a PFS benefit, independent of biomarker subgroups (hazard ratio &lt; 1.0), including estrogen receptor–negative and –positive subgroups. High HER2 protein, high HER2 and HER3 mRNA levels, wild-type PIK3CA, and low sHER2 showed a significantly better prognosis (P &lt; .05). PIK3CA showed the greatest prognostic effect, with longer median PFS for patients whose tumors expressed wild-type versus mutated PIK3CA in both the control (13.8 v 8.6 months) and pertuzumab groups (21.8 v 12.5 months). Conclusion Through comprehensive prospective analyses, CLEOPATRA biomarker data demonstrate that HER2 is the only marker suited for patient selection for the trastuzumab plus pertuzumab–based regimen in HER2-positive metastatic breast cancer. HER2, HER3, and PIK3CA were relevant prognostic factors.
Peer Review Is an Effective Screening Process to Evaluate Medical Manuscripts
Authors: Margaret Abby
Journal: JAMA (1994)

To measure the effectiveness of peer review as a screening process to evaluate medical manuscripts.Retrospective.The editorial office of the American Journal of Surgery (AJS).A MEDLINE search was conducted of publications from 1984 to 1992 for manuscripts that were identical or similar to those rejected by AJS between January and December 1989. Manuscripts that were submitted to AJS by foreign authors were excluded because of the presumed difficulty in tracking foreign-language publications.The percentage of manuscripts rejected by AJS that were subsequently published in journals indexed by MEDLINE, the time from rejection to ultimate publication, and the journal of publication. The reasons for rejection were also documented. We assumed that the majority of rejected manuscripts would be published within 3 years after rejection.One hundred twenty-five manuscripts submitted by North American authors were rejected by AJS in 1989, and 62% were not subsequently published in another core medical journal during the study period. The average duration between rejection and later publication was 17 months. Of those manuscripts subsequently published, 54% appeared in general surgical journals, including 12% that were revised, reevaluated, and later accepted by AJS. Twenty-nine percent of the rejected manuscripts were published in specialty medical journals, 10% in state and local journals, and the remainder in general medical journals. Twenty-eight percent of the authors of rejected manuscripts had previously and subsequently published manuscripts on very similar subjects.Our data indicate that the review process serves as a sieve and influences whether manuscripts are published in core medical journals. This was demonstrated by the fact that rejected manuscripts often were not published in other indexed medical journals.
Heroin Prescription and History
Authors: Virginia Berridge
Journal: New England Journal of Medicine (2009)

In this issue of the Journal, Oviedo-Joekes et al.1 report on the results of the North American Opiate Medication Initiative (NAOMI) trial comparing methadone with injectable diacetylmorphine (the active ingredient in heroin) for the treatment of heroin addiction. These data from North America point to a conclusion that has been widely supported, although not without controversy, by similar recent studies in Europe.2 The results of this trial may be added to those from Germany, the Netherlands, Spain, and Switzerland. Switzerland has 10 years of experience in the prescription of heroin, and in a November 2008 referendum, 68% of voters were . . .
Epidemiology of pollution‐induced airway disease in Scandinavia and Eastern Europe
Authors: B. BJÖRKSTÉN
Journal: Allergy (1997)

Björkstén B. Epidemiology of pollution‐induced airway disease in Scandinavia and Eastern Europe. Several potential environmental factors, particularly air pollutants, have been implicated as causal factors for the increased prevalence of allergic disease in western industrialized countries. However, even when combined, these factors can only partly explain the increase. Differences in prevalence of allergy are apparent between urban and rural areas of industrialized countries, with positive skin prick tests being more common in children living in urban regions. However, the prevalence of atopy is lower in children in central and Eastern Europe, where air pollution poses a major problem, than in Western Europe. Indeed, preliminary data from the International Study of Asthma and Allergy in Children (ISAAC) confirm that the prevalence of childhood atopy is lower in Eastern Europe than in Scandinavia. Although air pollution is undoubtedly associated with the development of allergic disease, other factors connected with western lifestyle, such as changes in diet and living conditions, may play an important role and provide a possible explanation for the higher prevalence of allergic disease in western industrialized countries.
Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor‐type chimerism: Report of two cases
Authors: Haruhiko Ohashi, Chiaki Kato, Shoko Fukami, Hidehiko Saito, Motohiro Hamaguchi
Journal: American Journal of Hematology (2005)

Abstract We studied two cases with leukemia that relapsed in the central nervous system (CNS) after allogeneic stem cell transplantation. One patient underwent peripheral blood stem cell transplantation (SCT) from a related, yet haplotype‐mismatched, donor for chronic myelomonocytic leukemia. She was kept in complete remission (CR) in the bone marrow (BM) for 7 months, until relapse in the cerebrospinal fluid (CSF) was evident. In the other patient, with acute lymphoblastic leukemia, systemic relapse occurred when he was still on immunosuppression 6 months after SCT from an unrelated donor. After induction chemotherapy following cessation of immunosuppression, the BM examination proved CR. During consolidation chemotherapy, however, he developed leukemic dissemination in the CSF, despite the fact that the BM was in CR. Chimerism status in the BM mononuclear cells and fractionated peripheral blood (PB) cells (granulocytes, T‐lymphocytes, and the others) was assessed by short tandem repeat analysis. In both patients, the BM cells and all the fractions of the PB cells proved donor‐type chimeras. These results seem to suggest that the graft‐versus‐leukemia effects might not be as effective in the CNS as in the BM, even when complete T‐lymphoid chimerism is achieved. Am. J. Hematol. 79:142–146, 2005. © 2005 Wiley‐Liss, Inc.
A Comparison of Live Counseling With a Web-Based Lifestyle and Medication Intervention to Reduce Coronary Heart Disease Risk
Authors: Thomas C. Keyserling, Stacey L. Sheridan, Lindy B. Draeger, Eric A. Finkelstein, Ziya Gizlice, Eliza Kruger, Larry F. Johnston, Philip D. Sloane, Carmen Samuel-Hodge, Kelly R. Evenson, Myron D. Gross, Katrina E. Donahue, Michael P. Pignone, Maihan B. Vu, Erika A. Steinbacher, Bryan J. Weiner, Shrikant I. Bangdiwala, Alice S. Ammerman
Journal: JAMA Internal Medicine (2014)

Most primary care clinicians lack the skills and resources to offer effective lifestyle and medication (L&M) counseling to reduce coronary heart disease (CHD) risk. Thus, effective and feasible CHD prevention programs are needed for typical practice settings.To assess the effectiveness, acceptability, and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats.A comparative effectiveness trial in 5 diverse family medicine practices in North Carolina. Participants were established patients, aged 35 to 79 years, with no known cardiovascular disease, and at moderate to high risk for CHD (10-year Framingham Risk Score [FRS], ≥10%).Participants were randomized to counselor-delivered or web-based format, each including 4 intensive and 3 maintenance sessions. After randomization, both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies. Participants chose the risk-reducing strategies they wished to follow.The primary outcome was within-group change in FRS at 4-month follow-up. Other measures included standardized assessments of blood pressure, blood lipid levels, lifestyle behaviors, and medication adherence. Acceptability and cost-effectiveness were also assessed. Outcomes were assessed at 4 and 12 months.Of 2274 screened patients, 385 were randomized (192 counselor; 193 web): mean age, 62 years; 24% African American; and mean FRS, 16.9%. Follow-up at 4 and 12 months included 91% and 87% of the randomized participants, respectively. There was a sustained reduction in FRS at both 4 months (primary outcome) and 12 months for both counselor-based (-2.3% [95% CI, -3.0% to -1.6%] and -1.9% [95% CI, -2.8% to -1.1%], respectively) and web-based groups (-1.5% [95% CI, -2.2% to -0.9%] and -1.7% [95% CI, -2.6% to -0.8%] respectively). At 4 months, the adjusted difference in FRS between groups was -1.0% (95% CI, -1.8% to -0.1%) (P = .03), and at 12 months, it was -0.6% (95% CI, -1.7% to 0.5%) (P = .30). The 12-month costs from the payer perspective were $207 and $110 per person for the counselor- and web-based interventions, respectively.Both intervention formats reduced CHD risk through 12-month follow-up. The web format was less expensive.clinicaltrials.gov Identifier: NCT01245686.
Plasma Cytokine and Angiogenic Factor Profiling Identifies Markers Associated with Tumor Shrinkage in Early-Stage Non–Small Cell Lung Cancer Patients Treated with Pazopanib
Authors: Petros G. Nikolinakos, Nasser Altorki, David Yankelevitz, Hai T. Tran, Shaoyu Yan, Dilip Rajagopalan, Walter Bordogna, Lone H. Ottesen, John V. Heymach
Journal: Cancer Research (2010)

There is an unmet need for pharmacodynamic and predictive biomarkers for antiangiogenic agents. Recent studies have shown that soluble vascular endothelial growth factor receptor 2 (sVEGFR2), VEGF, and several other soluble factors may be modulated by VEGF pathway inhibitors. We conducted a broad profiling of cytokine and angiogenic factors (CAF) to investigate the relationship between baseline CAF levels, CAF changes during treatment, and tumor shrinkage in early-stage non-small cell lung cancer (NSCLC) patients treated with pazopanib, an oral angiogenesis inhibitor targeting VEGFR, platelet-derived growth factor receptor, and c-kit. Plasma samples were collected before treatment and on the last day of therapy from 33 patients with early-stage NSCLC participating in a single-arm phase II trial. Levels of 31 CAFs were measured by suspension bead multiplex assays or ELISA and correlated with change in tumor volume. Pazopanib therapy was associated with significant changes of eight CAFs; sVEGFR2 showed the largest decrease, whereas placental growth factor underwent the largest increase. Increases were also observed in stromal cell-derived factor-1alpha, IP-10, cutaneous T-cell-attracting chemokine, monokine induced by IFN-gamma, tumor necrosis factor-related apoptosis-inducing ligand, and IFN-alpha. Posttreatment changes in plasma sVEGFR2 and interleukin (IL)-4 significantly correlated with tumor shrinkage. Baseline levels of 11 CAFs significantly correlated with tumor shrinkage, with IL-12 showing the strongest association. Using multivariate classification, a baseline CAF signature consisting of hepatocyte growth factor and IL-12 was associated with tumor response to pazopanib and identified responding patients with 81% accuracy. These data suggest that CAF profiling may be useful for identifying patients likely to benefit from pazopanib, and merit further investigation in clinical trials.
ECONOMICS OF MEDICAL ORGANIZATION.
Authors: J. MADISON TAYLOR
Journal: JAMA (1905)

The value of medical organization should be repeatedly emphasized, for it requires much repetition of its advantages to secure full co-operation. Medical men are prone to regard each other as rivals, not as colleagues, and this attitude must be abandoned before effective organization can be accomplished. A most harmful delusion is that best results follow independent or individual action; as a consequence of this, fluctuating personal views on medical treatment prevail, influencing the laity who, having apparently exhausted the resources of one man, reject him and select another. Each time a patient makes such a change, while being treated for some persistent disorder, less is expected, hope shrinks, and confidence dies, till at last the educated physician, equipped with knowledge and experience, is rejected and "mystery mongers" are consulted. These pretenders boast much and claim omniscience, and that most potent of remedies, suggestion, replaces skill and judgment. Again, many charlatans