tbuckley/cabot-search huggingface dataset:
AT-39A RANDOMIZED PHASE II TRIAL OF VANDETANIB (ZD6474) IN COMBINATION WITH CARBOPLATIN VERSUS CARBOPLATIN ALONE IN ADULTS WITH RECURRENT GLIOBLASTOMA
Authors: Katharine McNeill, Fabio Iwamoto, Teri Kreisl, Joohee Sul, Joanna Shih, Howard Fine
Journal: Neuro-Oncology (2014)

BACKGROUND: Vandetanib is a tyrosine kinase inhibitor of VEGFR-2, EGFR, and the RET oncogene. While vandetanib has not shown significant clinical activity, preclinical experience suggests synergistic efficacy in combination with carboplatin in glioblastoma (GBM). METHODS: This randomized non-comparative phase-II trial evaluates the efficacy and safety of vandetanib (300 mg/d NEIAED, 400 mg/d EIAED) in combination with carboplatin (AUC 6 q 4 weeks) versus carboplatin alone (AUC 6 q 4 weeks) in adults with recurrent GBM. Upon progression with single-agent carboplatin, single-agent vandetanib was offered. Contrast-enhanced-MRI before subsequent cycles were compared to baseline and response assessed using RANO criteria. Primary end-point was PFS-6. Ktrans, CBV, ADC, and HRQoL were measured before treatment and after 4 weeks and the relationship between these factors and time to progression and survival was explored. RESULTS: Thirty-two patients with recurrent GBM were accrued to each arm. Most frequent treatment related grade ≥ 3 toxicities were thrombocytopenia (n = 14), lymphopenia (n = 12), neutropenia (n = 7), seizure (n = 5), and hypertension (n = 4). There were two partial responses in the combination arm, none in the carboplatin arm. All patients had progressed at 6 months in the combination arm; one patient in the carboplatin arm was progression-free at 6 months. Median PFS and OS were 1.7 months (95% CI: 0.9 to 2.7 mo) and 5.6 months (95% CI: 4.6 to 8.6 mo) in the combination arm, and 0.9 months (95% CI: 0.89 to 0.92 mo) and 5.2 months (95% CI: 3.8 to 7.5 mo) in the carboplatin arm. Greater increase in ADC was predictive of shorter survival, and greater increase in CBV was predictive of shorter time to progression in both study arms. Changes in HRQoL were not predictive of time to progression or survival. CONCLUSIONS: The combination of vandetanib and carboplatin did not have significant activity in unselected patients with recurrent glioblastoma.
TCT-612 Two-Year Outcomes Following Implantation of 32mm and 38mm Platinum Chromium Everolimus Eluting Element Stents in Long Coronary Lesions
Authors: Paul Teirstein, Gregg Stone, Ian Meredith, Robert Feldman, Joseph Dens, Abram Rabinowitz, Christophe Dubois, Dominic Allocco, Keith Dawkins
Journal: Journal of the American College of Cardiology (2012)
Treating the traumatic memories of patients with dissociative identity disorder
Authors: R P Kluft
Journal: American Journal of Psychiatry (1996)

The author uses clinical experience informed by research findings to suggest approaches to the treatment of the traumatic memories of patients with dissociative identity disorder.Recent findings in the treatment of patients with this disorder and current considerations with regard to memories of childhood trauma are used to develop recommended approaches.Treatment of traumatic memories appears crucial in the recovery of patients with dissociative identity disorder, even though the reported memories may not be historically accurate. Criteria are available for determining whether a patient with the disorder is able to undertake such efforts, and methods such as fractionated abreaction have been developed to make the process less unsettling.Despite the difficulties posed by the vulnerability of patients with dissociative identity disorder to decompensation when working with traumatic material and the vicissitudes of autobiographical memory, modern therapeutic approaches allow the processing of such patients' traumatic material in a manner that reduces the likelihood of disruptive events and the misuse of recovered material.
Interleukin 2 targeted therapy in inflammatory bowel disease
Authors: S. Yarkoni, Y. Sagiv, A. Kaminitz, N. Askenasy
Journal: Gut (2009)

A series of excellent articles published recently in Gut have evaluated the role of T regulatory (Treg) cells in inflammatory bowel disease (IBD) and surrogate animal models.1 2 In principle, self-tolerance in autoimmune disorders may be restored either by specific interference with effector cells and molecular pathways involved in immune activation, or selective enhancement of suppressive cells and cytokines. Based on the long-standing recognition that interleukin 2 (IL2) is a significant stimulatory cytokine involved in immune activation, interference with IL2 signalling has been considered as a potential approach to arrest autoimmunity. Stimulated lymphocytes (B and cytotoxic T cells) secrete IL2 and express the IL2 receptor α chain (CD25) within a positive feedback loop of activation. More physiological approaches to reinstitution of self-tolerance surround the activity of suppressive immune cells, in particular, Treg cells, which prevent and even reverse ongoing autoimmune reactions.3 4 5 6 One particular potent subset of naturally occurring Treg cells is characterised by CD25 expression at high levels in conjunction with transcription factor X-linked forkhead/winged helix (FoxP3). It is not only a contextual relationship between CD25 and suppressive mechanisms, but ample supply of IL2 is essential to the development and function of these Treg cells, and inhibition of IL2 production by cytotoxic cells is one of the primary mechanisms of suppression. Therefore, disruption of IL2 signalling that tilts the equilibrium against suppressive elements evolves as a deleterious mechanism in the context of autoimmunity, rather than an immunosuppressive strategy. Consistently, mice deficient in IL2 …
MRCP: examining the obstructed bile duct
Authors: I T GILMORE
Journal: Gut (1998)

See article on page 680 

Clinicians have been taken aback by the rapid developments in magnetic resonance cholangiopancreatography (MRCP), including elegant computer reconstructions of the biliary and pancreatic ducts from images acquired by magnetic resonance scanning. Pioneer endoscopists of the late 1970s and 1980s struggled to produce diagnostic retrograde cholangiograms, at some risk to the patient, and now in the 1990s images of almost comparable quality can be produced without an endoscope, without contrast and even without radiation. The technical aspects are so complex that the non-radiologist is unlikely to understand the variations such as T2 spin weighting, half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences, and rapid acquisition with relaxation enhancement (RARE). For those wishing to try, they are clearly covered in a recent leading article in this journal.1 Yet the technique is so beguiling and the images so similar to those obtained with contrast injection that clinicians will have to be wary of serious errors of misinterpretation, particularly when viewing an image in …
Who Teaches the Neophyte?
Authors: Willis E. Brown
Journal: JAMA (1964)

IF ONE WERE TO ASK a member of the general public how a young man becomes a physician, his easy reply would be, "He goes to a medical school to learn how to be a doctor." Likewise, if the practicing physicians of this country were asked how one becomes a physician, they would doubtless reply that he would go to a medical school and study to be a doctor. Throughout most of the history of the healing arts, the education of the physician has been primarily through the preceptor-tutorial system. From time to time, formalized education courses have been available and utilized as part of this educational system. To learn the knowledge and skills of the healing art, it has been necessary and desirable that one apprentice himself to a successful practitioner. At approximately the turn of the century, formal medical education was primarily through proprietary schools, often for the personal aggrandizement
Genetic testing in the classroom
Authors: P. Jones, M. Billett, P. Scotting, S. Raeburn
Journal: BMJ (1995)

EDITOR,--Audrey Tyler and her colleagues are concerned that students' practical work could lead to genetic screening without pretest counselling.1 We have run such practicals for four years (for science students) and for two years (for medical students). Students are given the option of testing whether they are carriers of the defect causing cystic fibrosis (in terms of the δF-508 mutation) after an explanatory …
Bricanyl® Turbuhaler® and Ventolin® Rotahaler® in exercise‐induced asthma in children
Authors: J. M. Lopes Dos Santos, H. Costa, E. Ståhl, J. E. Wirén
Journal: Allergy (1991)

Bricanyl® Turbuhaler® (0.5 mg terbutaline sulphate) and Ventolin® Rotahaler® (0.4 mg salbutamol) were compared in a randomized double‐blind placebo controlled study on exercise‐induced asthma in 19 children (14 boys) aged 7‐14 years. The study was carried out on 3 separate days. Asthmatic attacks were provoked by free range running. Peak expiratory flow (PEF) was measured before and after exercise. If PEF decreased by &gt; 20 %, one inhalation from each of the inhalers was given under supervision of the investigator. Only one of the inhalers (none on the placebo day) delivered active drug. PEF was measured again 5 and 10 min after treatment. Already 5 min after treatment PEF had returned to baseline after active treatment. There was no statistically significant difference between the two active treatments. After placebo treatment, PEF did not return to baseline even at the 10 min post‐exercise measurement. Ten children needed extra medication after the last PEF measurement on the placebo day, whereas no child needed extra medication after any of the active treatments. No adverse events were reported in this study. In conclusion, Bricanyl Turbuhaler (0.5 mg) and Ventolin Rotahaler (0.4 mg) were equally efficacious in the treatment of exercise‐induced asthma in children.
A Rapid Method for Standardization of the Gated Radionuclide Left Ventricular Ejection Fraction
Authors: GARY L. PURNELL, BONNIE J. BAKER, MARVIN M. MURPHY, CHARLES M. BOYD, GLENN V. DALRYMPLE
Journal: Clinical Nuclear Medicine (1990)

Radionuclide ventriculography has become the standard method for serially evaluating left ventricular ejection fraction (EF). The "gold standard" for evaluating EF is the contrast ventriculogram, which uses mathematical models to arrive at the volumes used to calculate EF. These models are subject to possible error. This paper reports the standardization of volume measurements of a digital angiographic camera system using a series of cardiac phantoms and the correlation of measurement of the EF of a series of patients whose EF was determined by digital angiography and radionuclide ventriculography.
A Hitchhiker's guide to antisense and nonantisense biochemical pathways
Authors: A D Branch
Journal: Hepatology (1996)

Antisense pharmaceutical research has sought to provide drugs that would yield effective therapies for diseases resulting from the production of deleterious proteins. The original concept was straightforward: eliminate production of unwanted proteins, such as oncogenic proteins, by blocking the function of their mRNAs; and block their mRNAs by adding “antisense” nucleic acids that bind them through complementary base pairing. However, it has proven difficult to develop clinically useful antisense strategies. Conventional antisense nucleic acids are large, highly charged, complex molecules that interact with a wide variety of unintended cellular and microbial components, often causing “nonantisense effects.” It is now clear that a broad knowledge of nucleic acid biochemistry will be needed to optimize antisense molecules for use in patients. The efficacy of naturally occurring antisense molecules and the success of antisense agricultural strategies prove that antisense approaches can be powerful and specific. Pharmaceutical antisense research can be expected to yield many valuable products once sufficient information about antisense mechanisms has been gathered and applied. This article explains the biochemical events that give rise to both antisense and nonantisense effects and provides guidelines for designing and evaluating antisense experiments.
Wanted---more answers than questions: literature review
Authors: A S David
Journal: BMJ (2001)

The purpose of medical research is to advance knowledge and solve clinical problems. These high ideals are difficult to achieve. Instead, academia sometimes draws criticism for apparently doing research for its own sake. I therefore carried out a systematic literature review to examine whether published research was providing more questions than answers, or vice versa.

I used “more questions than answers” as a search term in the Medline database, spanning from 1966 to March 2001. To limit the potential number of hits, only the title and abstract were used as search fields. I also searched on the phrase “more answers than questions.” All article types were included if they had an English abstract.

Two terms occurred in 166 articles (reference list available on request). However, only three articles (0.018%) …
Results of a Home-Based Environmental Intervention among Urban Children with Asthma
Authors: Wayne J. Morgan, Ellen F. Crain, Rebecca S. Gruchalla, George T. O'Connor, Meyer Kattan, Richard Evans, James Stout, George Malindzak, Ernestine Smartt, Marshall Plaut, Michelle Walter, Benjamin Vaughn, Herman Mitchell
Journal: New England Journal of Medicine (2004)

Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma. The objective of this study was to determine whether an environmental intervention tailored to each child's allergic sensitization and environmental risk factors could improve asthma-related outcomes.We enrolled 937 children with atopic asthma (age, 5 to 11 years) in seven major U.S. cities in a randomized, controlled trial of an environmental intervention that lasted one year (intervention year) and included education and remediation for exposure to both allergens and environmental tobacco smoke. Home environmental exposures were assessed every six months, and asthma-related complications were assessed every two months during the intervention and for one year after the intervention.For every 2-week period, the intervention group had fewer days with symptoms than did the control group both during the intervention year (3.39 vs. 4.20 days, P<0.001) and the year afterward (2.62 vs. 3.21 days, P<0.001), as well as greater declines in the levels of allergens at home, such as Dermatophagoides farinae (Der f1) allergen in the bed (P<0.001) and on the bedroom floor (P=0.004), D. pteronyssinus in the bed (P=0.007), and cockroach allergen on the bedroom floor (P<0.001). Reductions in the levels of cockroach allergen and dust-mite allergen (Der f1) on the bedroom floor were significantly correlated with reduced complications of asthma (P<0.001).Among inner-city children with atopic asthma, an individualized, home-based, comprehensive environmental intervention decreases exposure to indoor allergens, including cockroach and dust-mite allergens, resulting in reduced asthma-associated morbidity.
Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy
Authors: R Avallone, M L Zeneroli, I Venturini, L Corsi, P Schreier, M Kleinschnitz, C Ferrarese, F Farina, C Baraldi, N Pecora, M Frigo, M Baraldi
Journal: Gut (1998)

Background/Aim —Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. Subjects —Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. Methods —Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N -desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. Results —Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. Conclusions —Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.
Accidental Intestinal Myiasis
Authors: I. M. Macgregor
Journal: BMJ (1945)

<h3>Abstract</h3> Non-vesicular lipid transport between bilayers at membrane contact sites plays important physiological roles. Mechanistic insight into the action of lipid transport proteins localized at these sites (bridge/tunnel versus shuttle models) requires a determination of the distance between bilayers at which this transport can occur. Here, we developed DNA-origami nanostructures to organize size-defined liposomes at precise distances and used them to study lipid transfer by the SMP domain of E-Syt1. Pairs of DNA ring-templated donor and acceptor liposomes were docked through DNA pillars, which determined their distance. The SMP domain was anchored to donor liposomes via an unstructured linker and lipid transfer was assessed via a FRET-based assay. We show that lipid transfer can occur over distances that exceed the length of SMP dimer, compatible with a shuttle model. The DNA nanostructures developed here can be adapted to study other processes occurring where two membranes are closely apposed to each other.
The Computer-Stored Medical Record
Authors: Ralph A. Korpman
Journal: JAMA (1988)

The medical record has grown in complexity to meet the many new demands for patient information. Computers have facilitated access to some information for some care providers, but automation has also highlighted the difficulty of designing an effective logic for a document with so many uses and users. In this issue ofTHE JOURNAL, McDonald and Tierney<sup>1</sup>review how a computer-stored medical record (CSMR) can aid physician practice, provided certain problems can be overcome.
The Effect of Adherence to Practice Guidelines on Depression Outcomes
Authors: Kimberly A. Hepner
Journal: Annals of Internal Medicine (2007)

Background: Few studies have assessed clinician adherence to depression practice guidelines and the relationship between clinician adherence and depression outcomes. Objective: To estimate how frequently specific guideline recommendations are followed and to assess whether following guideline recommendations is linked to improved depression outcomes. Design: Observational analysis of data collected from 1996 to 1998 in 3 randomized clinical trials. Setting: 45 primary care practices in 13 U.S. states. Patients: 1131 primary care patients with depression. Measurements: Expert panel methods were used to develop a patient survey–based index that measured adherence to clinical practice guidelines on depression. Rates of adherence to the 20 indicators that form the index were evaluated. Multivariable regression that controlled for case mix was used to assess how index scores predicted continuous and dichotomous depression measures at 12, 18, and 24 months. Results: Quality of care was high (clinician adherence ≥79%) for 6 indicators, including primary care clinician detection of depression. Quality of care was low (adherence, 20% to 38%) for 8 indicators, including management of suicide risk (3 indicators), alcohol abuse (2 indicators), and elderly patients; assessment of symptoms and history of depression; and treatment adjustment for patients who did not respond to initial treatment. Greater adherence to practice guidelines significantly predicted fewer depressive symptoms on continuous measures (P < 0.001 for 12 months, P < 0.01 for 18 months, and P < 0.001 for 24 months) and dichotomous measures (P < 0.05 for 18 and 24 months). Limitations: Data are based on patient self-report. Possible changes in practice since 1998 may limit the generalizability of the findings. Conclusions: Adherence to guidelines was high for one third of the recommendations that were measured but was very low for nearly half of the measures, pointing to specific needs for quality improvement. Guideline-concordant depression care appears to be linked to improved outcomes in primary care patients with depression.
Ecstasy and the dance of death.
Authors: J. A. Henry
Journal: BMJ (1992)

the short arm of chromosome 6.6 Autosomal recessive inheritance has been proposed as its mode of transmission,67 but further confirmation is awaited.At present it seems likely that other factors, possibly other genes, modify the expression of a juvenile myoclonic epilepsy gene on chromosome 6.The recognition that non-pharmacological factors, such as emotional stress, sleep deprivation, alcohol use, and menses, seem to precipitate seizures',3 allows patients to gain some control of their seizures; most patients, however, will require treatment with drugs.Unfortunately, no prospective, con- trolled studies of drug treatment for juvenile myoclonic epilepsy have been performed and current information on use of anticonvulsant drugs has been derived exclusively from retrospective studies and anecdotal reports.8Currently the drug of choice is sodium valproate,9 which completely suppresses seizures in 80-90% of patients.7 Treatment of those patients who respond poorly to valproate is difficult and often requires more than one antiepileptic drug.No other single drug stands out as the ideal second line agent.Though anecdotal reports suggest that most other anticonvulsant drugs may be helpful, overall results are disappointing.In many patients carbamazepine exacerbates myoclonus and juvenile myoclonic epilepsy.'"'3Juvenile myoclonic epilepsy usually persists throughout life, and patients in their seventh decade have been reported.Attempted drug withdrawal, even after complete suppression of seizures for two or more years, leads to relapses in 80-90% ofpatients.' 28 It is therefore important that a correct diagnosis is made so that patients with juvenile myoclonic epilepsy may be advised that treatment is usually required life long.
Disappearance of Streetcars
Authors: Hugh H. Hussey
Journal: JAMA (1975)

The special feature, "JAMA 75 Years Ago," has its devotees who read it with amusement when they note the foibles of our predecessors in medical practice, or with chagrin when they find that medical affairs have not improved much with the passage of time. The item in the Oct 20, 1975, issue of<i>JAMA</i>(p 294) was concerned with the need for control of the filthy habit of spitting in public places. The author, Elmer B. Borland, MD, observed in passing that Dickens characterized Americans as a nation of spitters, lacking the natural instinct of cleanliness. Borland continued: Five years ago, the writer read a paper before the Allegheny County Medical Society recommending restriction and regulation of the spitting habit. Nine of ten members who took part in the discussion agreed that restriction and regulation were needed. Six, however, of the nine thought any regulation impossible. "Women can, but men