tbuckley/cabot-search huggingface dataset:
A VISTA on PD-1H
Authors: Yang Liu
Journal: Journal of Clinical Investigation (2014)

Three years ago, two research groups independently identified a previously undescribed T cell cosignaling molecule; one referred to it as V-domain Ig suppressor of T cell activation (VISTA), and the other used the term programmed death-1 homolog (PD-1H). Recombinant and ectopically expressed PD-1H functions as a coinhibitory ligand for T cell responses. However, the function of endogenous PD-1H is not clear. In this issue of the JCI, Flies and colleagues demonstrate that endogenous PD-1H on both T cells and APCs serves as a coinhibitory molecule for T cell activation and provide further support for targeting PD-1H as a therapeutic strategy for transplantation and cancers.
Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients
Authors: Janet E. Brown, Richard J. Cook, Allan Lipton, Robert E. Coleman
Journal: Clinical Cancer Research (2012)

Survival is highly variable in women with bone metastases from breast cancer and prognostic factors are needed. We analyzed data from a phase III trial comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer and bone metastases to identify variables prognostic for overall survival.Patients who received ZOL (n = 435) with bone marker assessments and complete baseline data were included. Relative risks (RR) of death over 24 months were assessed using a stratified Cox regression analysis. A reduced model was generated using stepwise backward elimination until only significant (P < 0.05) variables remained.Only 5 of 19 variables analyzed remained significantly prognostic for survival in the reduced multivariate model. These included age more than 50 years (RR 1.78-2.53, P ≤ 0.01 for each decade >50 versus ≤ 50); Functional Assessment of Cancer Therapy-General (FACT-G) score less than 65 units (P < 0.05 vs. ≥ 75 units); impaired (PS ≥ 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG) performance status (RR 1.74, P < 0.01); prior versus no prior chemotherapy (RR 1.97; P < 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase ≥ upper limit of normal (ULN) but < 2 × ULN correlated with a two-fold increased risk of death, and LDH > 2 × ULN correlated with a six-fold increased risk of death versus LDH < ULN (P < 0.0001 for both). Baseline bone marker levels were not significantly correlated with survival after adjustment for other significant covariates.This retrospective analysis shows that LDH levels correlate strongly with survival in patients with bone metastases from breast cancer and confirms the relevance of previously described prognostic factors.
HIDA and Pseudosplenomegaly in Hydatid Cyst and Amebic Abscess of Liver
Authors: LAMK M. LAMKI, NEELA LAMKI
Journal: Clinical Nuclear Medicine (1981)

Tc-99m-HIDA and related compounds have been universally accepted for studying the hepatobiliary system. The authors describe yet another use of HIDA documented by three case reports. HIDA is taken up by the hepatocytes and not by the reticuloenthothelial system. Two patients are described, one with hydatid cyst and the second with amebic abscess of the liver, in whom splenomegaly was diagnosed clinically and confirmed by ultrasonography as well as by Tc-99m-tin colloid scan. HIDA imaging proved the spleens to be normal. A displaced right lobe of the liver in one case, and an enlarged left lobe in the other, led to this erroneous diagnosis, which the authors term “pseudosplenomegaly.” In the third patient, HIDA not only clarified the extent of the spleen, but also revealed a “cold” area in the left lobe of the liver. This was missed by the colloid scan because of the position of the “cold” area.
Coronary patency and its relation to contractile reserve in hibernating myocardium
Authors: James A. Fallavollita, Michael Logue, John M. Canty
Journal: Cardiovascular Research (2002)

Objectives: Recent clinical studies suggest that contractile reserve may occur in a minority of viable, chronically dysfunctional segments with reduced resting flow (hibernating myocardium). We hypothesized that epicardial artery patency might predict which segments have critically reduced subendocardial flow reserve and limited contractile reserve. Methods: Pigs were chronically instrumented with a fixed stenosis on the left anterior descending coronary artery (LAD) to produce hibernating myocardium. At least 3 months later, flow at rest and during adenosine vasodilation (microspheres), ventricular function and contractile reserve (contrast ventriculography), and 18F-2-deoxyglucose (FDG) deposition (ex vivo tissue counting) were quantified. Results: Hibernating myocardium (regional dysfunction with reduced resting perfusion) was present in animals with an occluded (n = 40) or patent (n = 19) LAD. Viability was confirmed by histology and FDG deposition. In collateral-dependent hibernating myocardium, subendocardial flow did not increase above baseline levels during epinephrine or adenosine stimulation, consistent with exhausted subendocardial flow reserve at rest. This was associated with limited contractile reserve and regionally increased FDG deposition. In contrast, subendocardial flow reserve was present in hibernating myocardium distal to a patent artery. Contractile reserve during epinephrine infusion in this group was significantly greater than in animals with an occluded artery. Conclusions: The physiology and metabolism of hibernating myocardium was dependent upon stenosis severity and its effects on subendocardial flow reserve. In collateral-dependent hibernating myocardium, contractile reserve was limited in the setting of exhausted subendocardial flow reserve, thus supporting the hypothesis that metabolic imaging may be preferable for determining viability distal to a complete occlusion.
239 Vascular endothelial growth factor plays a role in the formation of new vessels at earlier stage of hepatocarcinogenesis
Authors: S.H. Ryu, Y.-H. Chung, J.W. Kim, J.A. Kim, J.W. Shin, H.C. Lee, E. Yu, Y.J. Lee, Y.S. Lee, D.J. Suh
Journal: Journal of Hepatology (2004)
Evidence based medicine: does it make a difference?
Authors: Paul Glasziou
Journal: BMJ (2005)

Evidence based medicine: does it make a difference? Use wiselyEditor-The term "evidence based medicine" entered the scientific lexicon only a little more than a decade ago. 1 What caused its remarkable spread, and what are the implications of its broad and rapid diffusion?The team that coined the term at first considered using the phrase "scientific medicine" but rejected it because it implied that other approaches were by definition unscientific. 2However, critics have argued that the term evidence based medicine carries a similar moral valence and linguistic slipperiness. 3 Who could argue against the notion of providing care that integrates individual clinical skill and the best external evidence? 4 Originally developed as a method for teaching medical residents, evidence based medicine is being applied ever more broadly to the organisation and delivery of medical services.Multiple stakeholders now seek to assume its mantle for purposes that often contradict its original intent.Managers, equating lack of evidence with lack of effectiveness, use it as a rationale for cutting services.Industry generates evidence of questionable quality to promote its products.Medical researchers come to believe that they hold a monopoly on generating and interpreting evidence.Evidence based medicine, developed as a means of taming the unscientific and messy world of clinical practice, has itself entered the unscientific and messy world of politics. 5ike any technology, evidence based medicine carries risks and benefits and can be used appropriately or inappropriately.Overly inclusive definitions threaten to deprive the term of meaning, and unchecked use increases the risk of misuse.In the past decade, evidence based medicine has contributed much to how we teach, deliver, and think about clinical services.In the coming decade, we must continue to ensure that it is not only used widely but wisely.
Lectures on the Practice of Medicine
Authors: C. Murchison
Journal: BMJ (1872)

Painz.B. Co;es/situtionial Pyrexia.C. Deranged Ftunctionts of In- flamed Part.-7.'a;ieties.-8.Treatonezt.V. Causes-The causes of inflammation vary greatly.There are both predisposing and exciting causes.The exciting cause is some- thing that irritates the nerves of the tissue which becomes inflamed; and predisposing causes are those which dispose the tissue to suffer from this irritation.Of a given number of persons exposed to the same exciting cause of inflammation, in comparatively few does the cause take effect, and they are said to suffer in virtue of some predis- position; those also in whom the predisposition is great suffer more than those in whom it is slight.Again, the organ which becomes in- flamed varies according to the individual predisposition; and thus it is that cold will excite in one person tonsillitis, in a second pneumonia, in a third enteritis, and in a fourth inflammation of the kidneys.And lastly, the quality of the inflammation produced by the same exciting cause will vary with the specific predispositions of the individual ; in one it will be rheumatic, in a second gouty, in a third syphilitic, and in a fourth it will show a marked tendency to gangrene.A. T'he Predis.osingC(eases of inflammation may be grouped under four heads.i. il/orbidl Sltats of teie Blood and Tissues are among the most com- mon.
Smallpox: The Triumph over the Most Terrible of the Ministers of Death
Authors: Nicolau Barquet
Journal: Annals of Internal Medicine (1997)

More than 200 years ago, Edward Jenner performed an experiment that laid the foundation for the eradication of smallpox and transformed humankind's fight against disease. Smallpox afflicted humankind as no other disease had done; its persistence and diffusion were without parallel. The disease brought down at least three empires. Generations watched helplessly as their children succumbed to the disease or were disfigured or blinded by it. Attempts were made to contain smallpox by isolating its sufferers and, later, by using variolation with varying degrees of success. However, the definitive solution was not found until Jenner's work was done at the end of the 18th century. Milkmaids who had developed cowpox from contact with cow udders informed Jenner that they were protected from the human form of the disease; he listened to their folk wisdom and raised it to the status of scientific fact. Jenner did not discover vaccination, but he was the first to demonstrate that this technique offered a reliable defense against smallpox. It was also a reliable defense against other illnesses, such as poliomyelitis, measles, and neonatal tetanus, although this was not known in Jenner's lifetime.
DREAMING, DRAWING AND THE DREAM SCREEN IN THE PSYCHOANALYSIS OF A TWO-AND-A-HALF-YEAR-OLD BOY
Authors: J. COTTER HIRSCHBERG
Journal: American Journal of Psychiatry (1966)

Solomon has written about the change in emphasis from perceptual to conceptual thinking as being an important part of ego mastery, partly responsible for the establishment of autonomy(21). This paper suggests that a child's drawings, when they serve the function of a dream screen, manifest dream content on it. They can sometimes be used by the child as experimental soundings in the attempt to establish the self and separate from the parental figure, while continuing to maintain the necessary relationship with the mother, and will thus enable the child to struggle with oedipal conflict with a configuration of self-esteem. In summary, then, the analytic material in this case seemed to support the following theses: 1. The processes of "looking" and "seeing" help to mark the boundaries of reality for the very young child. 2. "Not looking" may be used in the same manner that the dream screen is used by adults: to cope with frustration which has both oral and genital determinants, and can sometimes be a regression to the primary process wish fulfillment of a return to mother's breast. 3. The very young child can sometimes most easily communicate his dreams by seeing them on the blank paper and then drawing them and adding the manifest dream content in this way. However, at other times the blank drawing paper functions as if it were a dream screen(14) and then represents the sated satisfaction of falling asleep at mother's breast, and the child produces associations only to the dream screen. These "blank dreams" cause no conscious anxiety, and associations to them may bring feelings of superiority and mild elation. 4. As the child improves and matures, the manifest dream content added on to the dream screen expresses oedipal conflict and the child's attempt at the oedipal solution. In these later instances looking and dreaming become functions of active mastery.
Dry haricot bean: a new continence aid for elderly men?
Authors: A Patel
Journal: BMJ (1990)

sometimes necessary to be a little thick skinned, not to say ruthless, to protect the interest of disabled people in wheelchairs.I wondered how parents of such children coped.On the other hand many of the places we visited welcomed us warmly,,even admitting us free or at a reduced rate.A lady who ran an orchid farm opened on her day off to receive us.All the children enjoyed the beach, including Christopher, who sunbathed in a deckchair supervising the building of sandcastles, with his portable ventilator on the sand beside him.Two of the girls went into the sea.Hauling wheelchairs to the edge of the sea across soft sand was hard work.An easier method with Victoria was to give her a piggy back ride to the sea.Once she was in the water it was quite easy to keep her afloat thanks to a foam lifejacket invented at Chailey.
Anomalous rearrangements of the immunoglobulin heavy chain genes in human leukemias support the loop-out mechanism of class switch.
Authors: M Laffan, L Luzzatto
Journal: Journal of Clinical Investigation (1992)

Discrete rearrangements of immunoglobulin genes are characteristic of lymphoproliferative diseases of B cells and provide direct evidence of their clonal nature. In addition, because leukemic transformation and growth may amplify B cell clones regardless of selection by antigen, analysis of rearranged Ig genes in leukemic clones may give insight into molecular events taking place during the ontogenesis of normal B cells. We have tested DNA samples from patients with chronic B cell leukemias in search for abnormal rearrangements of the Ig heavy chain gene region. By Southern blot analysis we found an unexpected break in the JH-C mu region in 7 out of 118 cases. Two of these cases were investigated in detail by constructing from each a phage genomic library and isolating the phage clones containing the break points. In both cases the JH-C mu separation was confirmed. Further analysis demonstrated that in both cases the abnormality was an inversion of the Ig heavy chain gene between C mu and one of the C gamma segments. This inversion structure strongly suggests that, as has been demonstrated in murine cell lines and in splenocytes stimulated in vitro, class switching in human B lymphocytes occurs in vivo via a loop-out deletion mechanism. The frequency of abnormal events may be as high as 15%. Our data indicate that a proportion of cases of chronic B cell leukemia arise from a cell which has attempted an Ig class switch.
Involving patients in the <i>BMJ</i>
Authors: Peter Lapsley, Fiona Godlee
Journal: BMJ (2007)

<h3>Background</h3> Prevalence of people with multimorbidity rises. Multimorbidity constitutes a challenge to the healthcare system, and treatment of patients with multimorbidity is prone to high-quality variations. Currently, no set of quality indicators (QIs) exists to assess quality of care, let alone incorporating the patient perspective. We therefore aim to identify aspects of quality of care relevant to the patients’ perspective and match them to a literature-based set of QIs. <h3>Methods</h3> We conducted eight focus groups with patients with multimorbidity and three focus groups with patients’ relatives using a semistructured guide. Data were analysed using Kuckartz’s qualitative content analysis. We derived deductive categories from the literature, added inductive categories (new quality aspects) and translated them into QI. <h3>Results</h3> We created four new QIs based on the quality aspects relevant to patients/relatives. Two QIs (patient education/self-management, regular updates of medication plans) were consented by an expert panel, while two others were not (periodical check-ups, general practitioner-coordinated care). Half of the literature-based QIs, for example, assessment of biopsychosocial support needs, were supported by participants’ accounts, while more technical domains regarding assessment and treatment regimens were not addressed in the focus groups. <h3>Conclusion</h3> We show that focus groups with patients and relatives adding relevant aspects in QI development should be incorporated by default in QI development processes and constitute a reasonable addition to traditional QI development. Our QI set constitutes a framework for assessing the quality of care in the German healthcare system. It will facilitate implementation of treatment standards and increase the use of existing guidelines, hereby helping to reduce overuse, underuse and misuse of healthcare resources in the treatment of patients with multimorbidity. <h3>Trial registration number</h3> German clinical trials registry (DRKS00015718), Pre-Results.
Vertigo and Imbalance
Authors: H. Ludman
Journal: BMJ (2014)

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### Overview

Vertigo is caused by vestibular disturbance and is the result of: 

Vertigo, by definition, is an illusion of movement, of the patient or the surroundings. The origin of the name suggests a sense of rotational movement, but should apply to any direction of movement experienced. Imbalance always accompanies vertigo, but is not always due to vertigo and is not a synonym. Imbalance occurs for many reasons without vertigo.

Normal balance needs:



Figure 1  
Sensory and motor components of balance.



Defects in any of these impair balance—with or without vertigo.

Vertigo arises if information from vestibular sources conflicts with data from the other sensory systems, or when a disordered central integration system in the brain does not correctly relate the body's movements to the vestibular input. Vertigo is always a symptom of vestibular defect . This may lie in the labyrinth (peripheral) or in its connections within the brain (central). When severe, it is accompanied by nausea and vomiting.

Vertigo is caused by: (a) peripheral vestibular disorders (labyrinthine); (b) middle ear infections spreading to the labyrinth; …
Long-term Transgene Expression in the Central Nervous System Using DNA Nanoparticles
Authors: David M Yurek, Anita M Fletcher, George M Smith, Kim B Seroogy, Assem G Ziady, Joseph Molter, Tomasz H Kowalczyk, Linas Padegimas, Mark J Cooper
Journal: Molecular Therapy (2009)

This study demonstrates proof of concept for delivery and expression of compacted plasmid DNA in the central nervous system. Plasmid DNA was compacted with polyethylene glycol substituted lysine 30-mer peptides, forming rod-like nanoparticles with diameters between 8 and 11 nm. Here we show that an intracerebral injection of compacted DNA can transfect both neurons and glia, and can produce transgene expression in the striatum for up to 8 weeks, which was at least 100-fold greater than intracerebral injections of naked DNA plasmids. Bioluminescent imaging (BLI) of injected animals at the 11th postinjection week revealed significantly higher transgene activity in animals receiving compacted DNA plasmids when compared to animals receiving naked DNA. There was minimal evidence of brain inflammation. Intrastriatal injections of a compacted plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) resulted in a significant overexpression of GDNF protein in the striatum 1-3 weeks after injection.
Discontinuation of Chemoprophylaxis against <i>Pneumocystis carinii</i> Pneumonia in Patients with HIV Infection
Authors: Bienvenido G. Yangco, Jennifer C. Von Bargen, Anne C. Moorman, Scott D. Holmberg
Journal: Annals of Internal Medicine (2000)

Background: HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). Objective: To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. Design: Nonrandomized prospective cohort study. Setting: 10 HIV clinics in eight U.S. cities. Patients: 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. Measurements: Incidence of PCP. Results: Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower viral loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). Conclusions: Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients. *For members of the HIV Outpatient Study Investigators, see Appendix.
Should One Reinsert the Stylet during Lumbar Puncture?
Authors: Michael Strupp, Thomas Brandt
Journal: New England Journal of Medicine (1997)

To the Editor: The post–lumbar puncture syndrome may be due to prolonged leakage of cerebrospinal fluid because of delayed closure of a dural defect, which causes low cerebrospinal fluid pressure. The reported frequency of the syndrome ranges from less than 1 percent to 70 percent. Its incidence depends on the diameter of the needle,1 the shape of the needle,2 and whether a diagnostic lumbar puncture is performed or spinal anesthesia is administered.3 The incidence of the post–lumbar puncture syndrome is much lower after spinal anesthesia than after diagnostic lumbar puncture.3,4 The reason for this difference may be that a . . .
Step 2 Regimens in Hypertension
Authors: Frank A. Finnerty
Journal: JAMA (1979)

A single-blind clinical trial compared step 2 combination therapy consisting of 50 or 100 mg of hydroflumethiazide plus either 0.125 to 0.250 mg of reserpine, 500 to 2,000 mg of methyldopa, or 80 to 320 mg of propranolol hydrochloride, in 59 patients whose elevated blood pressure (BP) failed to respond adequately to the thiazide alone. After nine weeks of treatment, diastolic BP was reduced below 90 mm Hg in all 20 patients treated with the reserpine-hydroflumethiazide combination, in 13 of the 19 patients treated with methyldopa and hydroflumethiazide, and in 16 of the 20 patients treated with propranolol and hydroflumethiazide. Changes in laboratory values were not substantial; adverse reactions occurred only in the methyldopa group. Although the three treatment regimens were similar with respect to safety and efficacy, the reserpine-hydroflumethiazide combination offers the advantages of more convenient dosage at lower cost. (<i>JAMA</i>241:579-581, 1979)