tbuckley/cabot-search huggingface dataset:
Therapeutic Granulocyte Transfusions for Documented Infections
Authors: DREW J. WINSTON
Journal: Annals of Internal Medicine (1982)

Patients with granulocytopenia (granulocyte count less than 0.5 X 109/L) and a documented infection were randomized to receive or not to receive daily granulocyte transfusions in addition to antimicrobial therapy. Thirty-four of 47 control patients responded to therapy compared to 30 of 48 transfused patients (type 2 error, p = 0.02). Among patients with gram-positive septicemia, pneumonia, or a soft tissue infection, respective response rates for the control and transfused patients were 11 of 11 and 11 of 16 (Yates' corrected chi-squared test, p = 0.12). Response rates for patients with gram-negative septicemia were lower but were influenced by recovery of bone marrow function. Eleven of 12 control patients and seven of seven transfused patients with recovery of marrow function survived the gram-negative septicemia. In contrast, 12 of 24 control patients and 12 of 25 transfused patients survived gram-negative septicemia and persistent granulocytopenia (type 2 error, p = 0.13). Two thirds of all fatal infections were associated with an underlying disease refractory to medical therapy. Therapeutic granulocyte transfusions had no substantial benefit over optimal antimicrobial therapy alone in managing infected patients with granulocytopenia.
Cowpox virus in a 12-year-old boy: rapid identification by an orthopoxvirus-specific polymerase chain reaction.
Authors: P. Schupp, M. Pfeffer, H. Meyer, G. Burck, K. Kolmel, C. Neumann
Journal: British Journal of Dermatology (2001)

Although smallpox was eradicated 20 years ago, other members of the genus Orthopoxvirus (OPV), such as cowpox virus (CPXV) or monkeypox virus, are still a threat to humans. Because human CPXV infection is rare, it is seldom suspected on clinical grounds only. We report a boy who presented with two necrotic ulcers with surrounding erythema. Infection with OPV was suspected, as antibiotic treatment had not produced improvement and smears were negative for anthrax. An OPV was isolated and an OPV-specific polymerase chain reaction combined with a subsequent restriction enzyme fragment length polymorphism assay confirmed infection by CPXV. Although the patient's cat had had no skin lesions, OPV-specific antibodies were found at a titre of 1 : 8 in a plaque reduction assay, suggesting that the cat had transmitted the virus to the boy.
Semaphorin SEMA3F Affects Multiple Signaling Pathways in Lung Cancer Cells
Authors: Vincent A. Potiron, Girish Sharma, Patrick Nasarre, Jonathan A. Clarhaut, Hellmut G. Augustin, Robert M. Gemmill, Joëlle Roche, Harry A. Drabkin
Journal: Cancer Research (2007)

Abstract Loss of SEMA3F occurs frequently in lung cancer and correlates with advanced stage of disease. We previously reported that SEMA3F blocked tumor formation by H157 lung cancer cells in a rat orthotopic model. This was associated with loss of activated αVβ3 integrin, impaired cell adhesion to extracellular matrix components, and down-regulation of phospho-extracellular signal-regulated kinase 1/2 (ERK1/2). These results suggested that SEMA3F might interfere with integrin outside-in signaling. In the present report, we found that SEMA3F decreased adhesion to vitronectin, whereas integrin-linked kinase (ILK) kinase activity was down-regulated in SEMA3F-expressing H157 cells. Exposure to SEMA3F-conditioned medium led to diminution of phospho-ERK1/2 in four of eight lung cancer cell lines, and ILK silencing by small interfering RNA led to similar loss of phospho-ERK1/2 in H157 cells. Moreover, SEMA3F expression (with constitutive and inducible systems) also reduced AKT and signal transducer and activator of transcription 3 (STAT3) phosphorylation independently of ILK-ERK1/2. These signaling changes extended downstream to hypoxia-inducible factor-1α (HIF-1α) protein and vascular endothelial growth factor (VEGF) mRNA levels, which were both reduced in three of four SEMA3F-transfected cell lines. Mechanistically, the effects on HIF-1α were consistent with inhibition of its AKT-driven protein translation initiation, with no effect on HIF-1α mRNA level or protein degradation. Furthermore, when H157 cells were injected s.c. in nude mice, tumors derived from SEMA3F-expressing cells showed lower microvessel density and tumor growth. These results show that SEMA3F negatively affects ILK-ERK1/2 and AKT-STAT3 signaling, along with inhibition of HIF-1α and VEGF. These changes would be anticipated to contribute significantly to the observed antitumor activity of SEMA3F. [Cancer Res 2007;67(18):8708–15]
National Blood Authority.
Authors: J Cash
Journal: BMJ (1993)

paradoxical that the UN sent its troops to protect the people in the UN protected areas while its officials have no open access to the civilian population.Altogether 1626 people were expelled after the arrival of the UN protective force in the east sector, and the force admits that at least 500 people have been killed by Serbian paramilitary forces.We call on the international community, particularly doctors, to help in protecting the lives of these people now, when the winter has closed in on the starving, sick, young, and old.The presence of representatives of the international community and humanitarian organisations is necessary to protect the population.Although their presence may not be sufficient to prevent violations of the humanitarian law and abuses of the civilian popu- lation, their neutrality and independence may help "to defend those it assists, to keep them from dying of hunger, to protect them from ill-treatment, to make sure they do not 'disappear' and that they are not attacked" (J-L Blondel, extracts from the International Review of the Red Cross, Sept-Oct 1987).
Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis
Authors: Norma Adán, Jessica Guzmán-Morales, Maria G. Ledesma-Colunga, Sonia I. Perales-Canales, Andrés Quintanar-Stéphano, Fernando López-Barrera, Isabel Méndez, Bibiana Moreno-Carranza, Jakob Triebel, Nadine Binart, Gonzalo Martínez de la Escalera, Stéphanie Thebault, Carmen Clapp
Journal: Journal of Clinical Investigation (2013)

Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3–dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor–null (Prlr–/–) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.
Anaphylactoid Shock from Blood Exchange as a Factor in Experimental Cardiopulmonary Bypass
Authors: N. A. J. Hamer, J. F. Dickson, J. W. Dow, H. L. Gadboys
Journal: Thorax (1959)

During 75 cardiopulmonary bypass experiments in dogs, a fall in arterial pressure or a tendency for the animal to take up blood from the extra- corporeal circuit was noted at the onset of perfusion.To determine the mechanism of these reactions, the effect of homologous blood exchange in the dog was studied using a variety of techniques, including total and partial cardiac bypass.METHODS In the 75 preliminary total cardiopulmonary bypass studies a vertical-screen oxygenator and rotary pumps were used.The priming volume was approximately 3 litres and blood from four or five donors was required.Subsequent total bypass experiments were performed with a rotating-disc oxygenator and a pump driven by compressed air (Hufnagel, McAlinden, Vardar, DeVenecia, and Real, 1958).The volume of this circuit was somewhat smaller and only three donors were needed in most experiments.The two partial cardiac bypass techniques used were veno-arterial pumping and left heart bypass.Veno- arterial pumping consists of transferring the superior vena caval return to the lower aorta without oxygen- ation (Hamer, Dickson, and Dow, 1959), and left heart bypass involves pumping oxygenated blood from the left atrium to the aorta.A simple circuit with a closed venous reservoir and a capacity of 800 ml. was used for both these procedures, and was usually filled with blood from one donor.Blood exchange with constant volume was performed by placing 200 ml. of blood from each of one to four donor animals in a closed flask suspended above the recipient and connected to cannulae in the femoral artery and vein.When the cannulae were opened pressure in the flask rose 25 to 30 mm.Hg and blood exchange occurred, the volume of blood in the flask increasing by less than 50 ml.Mongrel dogs weighing 15 to 25 kg.were used throughout.Donor blood was obtained from animals lightly anaesthetized with pentothal (15 mg./kg.body weight) by arterial exsanguination into bottles
Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease
Authors: Shichun Tu, Shu-ichi Okamoto, Stuart A Lipton, Huaxi Xu
Journal: Molecular Neurodegeneration (2014)

Alzheimer's disease (AD) is a devastating disease characterized by synaptic and neuronal loss in the elderly. Compelling evidence suggests that soluble amyloid-β peptide (Aβ) oligomers induce synaptic loss in AD. Aβ-induced synaptic dysfunction is dependent on overstimulation of N-methyl-D-aspartate receptors (NMDARs) resulting in aberrant activation of redox-mediated events as well as elevation of cytoplasmic Ca2+, which in turn triggers downstream pathways involving phospho-tau (p-tau), caspases, Cdk5/dynamin-related protein 1 (Drp1), calcineurin/PP2B, PP2A, Gsk-3β, Fyn, cofilin, and CaMKII and causes endocytosis of AMPA receptors (AMPARs) as well as NMDARs. Dysfunction in these pathways leads to mitochondrial dysfunction, bioenergetic compromise and consequent synaptic dysfunction and loss, impaired long-term potentiation (LTP), and cognitive decline. Evidence also suggests that Aβ may, at least in part, mediate these events by causing an aberrant rise in extrasynaptic glutamate levels by inhibiting glutamate uptake or triggering glutamate release from glial cells. Consequent extrasynaptic NMDAR (eNMDAR) overstimulation then results in synaptic dysfunction via the aforementioned pathways. Consistent with this model of Aβ-induced synaptic loss, Aβ synaptic toxicity can be partially ameliorated by the NMDAR antagonists (such as memantine and NitroMemantine). PSD-95, an important scaffolding protein that regulates synaptic distribution and activity of both NMDA and AMPA receptors, is also functionally disrupted by Aβ. PSD-95 dysregulation is likely an important intermediate step in the pathological cascade of events caused by Aβ. In summary, Aβ-induced synaptic dysfunction is a complicated process involving multiple pathways, components and biological events, and their underlying mechanisms, albeit as yet incompletely understood, may offer hope for new therapeutic avenues.
Molecular Evolution of the Wingless Gene and Its Implications for the Phylogenetic Placement of the Butterfly Family Riodinidae (Lepidoptera: Papilionoidea)
Authors: Dana L. Campbell, Andrew V. Z. Brower, Naomi E. Pierce
Journal: Molecular Biology and Evolution (2000)

The sequence evolution of the nuclear gene wingless was investigated among 34 representatives of three lepidopteran families (Riodinidae, Lycaenidae, and Nymphalidae) and four outgroups, and its utility for inferring phylogenetic relationships among these taxa was assessed. Parsimony analysis yielded a well-resolved topology supporting the monophyly of the Riodinidae and Lycaenidae, respectively, and indicating that these two groups are sister lineages, with strong nodal support based on bootstrap and decay indices. Although wingless provides robust support for relationships within and between the riodinids and the lycaenids, it is less informative about nymphalid relationships. Wingless does not consistently recover nymphalid monophyly or traditional subfamilial relationships within the nymphalids, and nodal support for all but the most recent branches in this family is low. Much of the phylogenetic information in this data set is derived from first- and second-position substitutions. However, third positions, despite showing uncorrected pairwise divergences up to 78%, also contain consistent signal at deep nodes within the family Riodinidae and at the node defining the sister relationship between the riodinids and lycaenids. Several hypotheses about how third-position signal has been retained in deep nodes are discussed. These include among-site rate variation, identified as a significant factor by maximum likelihood analyses, and nucleotide bias, a prominent feature of third positions in this data set. Understanding the mechanisms which underlie third-position signal is a first step in applying appropriate models to accommodate the specific evolutionary processes involved in each lineage.
Mirage of Health
Authors: William J. Hossley
Journal: JAMA (1962)

To the Editor:—  This is a letter of protest about your printing inThe Journal( 177 :907 [Sept. 30] 1961) an endorsed  entitled Non-Hereditary Protective Reactions. The portion of the article with which I disagree most violently, both as to its context and also to its impressions on the reader if quoted in the newspapers, as so much ofThe Journalis, reads as follows: In a not too-distant past children were expendable. Many more were produced than were needed to keep the species going, a situation which still prevails in most of the world. As a result of effective birth control and of changed ethics, however, it is now desired that all children survive.  The intent of the author, I hope, was not what I have interpreted this to mean. The possible impressions which might be derived from this quotation are, however, legion. I will not burden you
Lymphoscintigraphy in Angiomyomatous Hamartomas and Primary Lower Limb Lymphedema
Authors: Pierre Bourgeois, Jean-Louis Dargent, Denis Larsimont, Denis Munck, Francois Sales, Magda Boels, Christine De Valck
Journal: Clinical Nuclear Medicine (2009)

Angiomyomatous hamartoma (AH) of the lymph node is a rare vascular benign disease of unknown etiology with a predisposition for the lymph nodes of the inguinal area. Only 18 cases have been described up to now in the literature and the disorder was reported to be associated with lymphedema or swelling of the ipsilateral limb in 4 patients. However, scintigraphic investigation of the lymphatic system in these patients was reported in only 2 cases.Five patients where the biopsy of inguinal nodes for suspected lymphadenitis led to the diagnosis of angiomyomatous hamartoma were investigated using lymphoscintigraphic techniques (1 girl aged 15; 1 boy aged 9 at the time of first biopsy and 11 at the time of the second one; and 3 men aged 30, 50, and 57). The operated limb was lymphedematous in 3 and 1 developed lymphedema after biopsy. The fifth patient developed a contralateral lymphedema after his second nodal biopsy.In all cases, lymphoscintigraphic investigation of the limbs showed extensive lymph node abnormalities on the operated side and in 4 cases on the opposite side.These observations support not only the hypothesis that lymphatic disturbance was involved in the pathogenesis of these tumors but also the proposition that lymphoscintigraphy should be performed in cases of inguinal lymphadenitis of unknown origin to diagnose the underlying situation of latent lymphedema.
Liver Procurement for Orthotopic Transplantation: An Analysis of the Pittsburgh Experience
Authors: David H. Van Thiel, Robert R. Schade, Thomas R. Hakala, Thomas E. Starzl, Donald Denny
Journal: Hepatology (1984)

The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined.
The Doctor-Patient-Family Relationship: A Compensatory Alliance
Authors: S R Hahn, J S Feiner, E H Bellin
Journal: Annals of Internal Medicine (1988)

Patients request health care for reasons that transcend the management of medical disease. Patients seek to create an "alliance" with the physician which "compensates" for conflict or deficit in the family system. This is particularly true for "problem," "difficult," or "hateful" patients who have significant psychosocial problems. When such a compensatory alliance evolves, it may become dysfunctional, limiting the physician's ability to make necessary medical interventions. By not explicitly including other family members, the traditional dyadic model of the doctor-patient relationship predisposes towards the formation of a compensatory alliance. The nature of the dysfunctional compensatory alliance may even remain obscure because the patient presents a distorted picture of the family situation. Therefore, to manage the compensatory alliance, the physician must perform a simple family assessment, including direct communication with other family members, early in the formation of the doctor-patient relationship. The physician should be alert to the formation of a dysfunctional compensatory alliance and the need to perform a family assessment whenever a patient explicitly or implicitly makes a request that engages the doctor with another family member. Recognition that a patient is "difficult" or awareness of a sense of helplessness, and frustration in caring for a patient may also indicate formation of a dysfunctional compensatory alliance and the need for family assessment. Recognizing key aspects of the doctor-patient-family relationship will enable the clinician to manage the compensatory alliance in a productive and therapeutic fashion. When family dysfunction requiring significant change is discovered, involvement of a family therapist should be offered.
Association of Elevated α<sub>1</sub>-Antichymotrypsin With Cognitive Impairment in a Prospective Study of the Very Old
Authors: Steven M. Gabriel, Deborah B. Marin, Paul S. Aisen, Melinda Lantz, Larry D. Altstiel, Kenneth L. Davis, Richard C. Mohs
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors investigated the relationships between concentrations of two acute-phase proteins, α1-antichymotrypsin (ACT) and α2-macroglobulin (MAC), and cognitive impairment in the very old. METHOD: Concentrations of ACT and MAC were determined in a prospective study using sera from medically stable elderly nursing home residents. Cognitive impairment was assessed with the Mini-Mental State. RESULTS: Concentrations of ACT were associated with greater cognitive impairment, as reflected by lower Mini-Mental State scores. This relationship did not exist for MAC. CONCLUSIONS: These data extend previous reports that patients with Alzheimer's disease have greater concentrations of ACT in their blood by demonstrating in a diagnostically diverse nursing home population a relationship between serum ACT and mental status. Elevated serum ACT in patients with compromised mental status may reflect a cerebral acute-phase response.
Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinaemia vasculitis
Authors: D Saadoun, M Resche-Rigon, D Sene, L Perard, A Karras, P Cacoub
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) α2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis. <h3>Methods:</h3> Sixteen consecutive patients with severe HCV-MC vasculitis that were resistant (n = 11) or relapser (n = 5) to a previous combination treatment with standard (n = 10) or Peg-IFNα2b (n = 6) plus ribavirin were included. They were treated with rituximab (375 mg/m<sup>2</sup> intravenously weekly for 4 weeks) combined with Peg-IFNα2b (1.5 μg/kg per week subcutaneously) plus ribavirin (600–1200 mg/day orally) for 12 months. <h3>Results:</h3> Fifteen patients (93.7%) showed clinical improvement, 10 of whom (62.5%) were clinical complete responders (CR). HCV RNA and serum cryoglobulin became undetectable in all the clinical CR. Peripheral blood B cell depletion was achieved in all patients (CD19+ cells, 111 (SD 32)/mm<sup>3</sup> at baseline versus 2(2)/mm<sup>3</sup> after the fourth infusion of rituximab) with reconstitution starting at the end of antiviral treatment. Compared with clinical CR, the partial or non-responders had a 3.6 times longer duration of vasculitis prior to treatment and a lower rate of early virological response. Treatment was well tolerated with no infectious complications. After a mean follow-up of 19.4 (SD 3.6) months, two patients experienced clinical relapse associated with a simultaneous reappearance of HCV RNA and cryoglobulin and an increase in the number of B cells. <h3>Conclusions:</h3> Rituximab combined with Peg-IFNα2b-ribavirin represents a safe and effective treatment option in severe refractory HCV-MC vasculitis.
THE USE OF EPINEPHRIN IN OCULAR HYPERTENSION
Authors: Harry S. Gradle
Journal: JAMA (1925)

Since Hamburger reopened the question of the local use of epinephrin for the purpose of reducing increased intra-ocular tension, the literature has been replete with many a pro and con on that subject. All investigators have injected the solution subconjunctivally, and only recently has mention been made by Thiel of the use of an epinephrin ointment. For the last few months, I have been using epinephrin for the relief of increased intra-ocular tension by topical application, with results that are just as effective as when the solution is injected underneath the conjunctiva. A small pledget of cotton is moistened with the same amount of epinephrin that would be used for subconjunctival injection (from 4 minims to 0.5 c.c.), and with fine forceps is introduced well under the upper eyelid. The eye may or may not be anesthetized previously with a drop of butyn or phenacain, depending on the ocular condition