tbuckley/cabot-search huggingface dataset:
Discussion on: The Pathology and Nomenclature of Hodgkin's Disease
Authors: Henry Rappaport
Journal: Cancer Research (1966)

The correlation of the histologie features of  disease with its clinical progress and its response to therapy presents a challenge to pathologists as well as to therapists. Dr. Lukes' very interesting data tend to indicate that within each clinical stage certain histologie types are indicative of a better prognosis than others. Based on this premise a subclassification has been proposed that adds to the complexity of the problem but at the same time emphasizes certain observations, some of them pre viously reported (1, 5, 7), that are of great interest: (a) that abundance of mature, well-differentiated lymphocytes in tissue sections is of favorable prognostic significance; (6) that, in general, lymphocytic depletion, whether associated with diffuse fibrosis or marked proliferation of Sternberg-Reed cells and other malignant histiocytes, indicates a bad prognosis; (c) that 1 form of fibrosis that has been designated as nodular sclerosis is often associated with long patient survival (2, 6, 8) even though there is lymphocytic depletion. In the discussion of the pathology of Hodgkin's, 3 major problems arise: (a) Why do we regard  disease as a neoplasm? (6) What is the possible biologic significance of the great variations in the histologie appearance of  disease? (c) What are the histologie criteria that enable us to diagnose  disease as a progressive neoplastia disorder? Even though Dr. Lukes is not fully convinced that every variant or type of  disease is necessarily a neoplasm, a common denominator does exist in all types of  disease in the form of atypical reticulum cells that appear to be neoplastic cells by generally accepted cytologie criteria. Some or many of them are the diagnostic Sternberg-Reed cells with multiple or inultilobed nuclei; others are mononuclear cells with similar nuclear chromatin structures. Almost invariably this neoplastic cellular proliferation is associated with a presumably reactive process that is composed of differentiated lymphocytes, plasma cells, eosinophilic and neutrophilic segmented granulocytes, histiocytes, and fibroblasta. The relative numerical proportions of these cell types vary and so do the ratios of neoplastic and inflammatory elements. When the reactive cellular proliferation is purely or almost purely lymphocytic, the term paragranuloma has been employed. When inflammatory elements are scant or lacking, the term Hodgkin's  is applicable. All other variants of  disease have been grouped together under the term Hodgkin's granuloma, representing roughly 90% of all instances of  disease. Dr. Lukes has shown that between the 2 extremesâ€”namely,  paragranuloma, on one end of the spectrum, and  sarcoma on the otherâ€”a considerable morphologic heterogenicity exists, with a particularly wide range in the ratio of lymphocytes to neoplastic histiocytes. Of great interest is the
GPs must have more consultation time with patients, college says
Authors: A. O'Dowd
Journal: BMJ (2010)

GPs want and need to spend more time with patients during their consultations, says the Royal College of General Practitioners (RCGP).

The college, launching a UK wide manifesto for patient care in anticipation of the imminent general election, called for longer consultation times, particularly with those patients who have more serious conditions. It also backed the call by the Royal College of Physicians to ban smoking in cars, though the GPs restricted their call to cars carrying children ( BMJ 2010;340:673, 27 March, doi:10.1136/bmj.c1689). 

It set out several recommendations for future care for patients, regardless of which political party wins the general election.

The average consultation time could …
Family berates doctor for refusing to follow law and remove feeding tube from woman in a coma
Authors: A. Garcia Rada
Journal: BMJ (2011)

Ramona Estevez, a woman aged 91 with Parkinson’s disease and in an irreversible coma after a massive stroke, died on 6 September 14 days after doctors were told by the government of the autonomous community of Andalusia to remove her feeding tube.

This is the first time that a public administration in Spain has had to intervene and force doctors to abide by the law.

Ms Estevez had repeatedly expressed her desire not to die suffering, although she had not put her wishes down in writing. The doctor attending her at the Hospital Blanca Paloma of Huelva refused to remove her feeding tube forcing her …
Ragweed-specific antibodies in bronchoalveolar lavage fluids and serum before and after segmental lung challenge: IgE and IgA associated with eosinophil degranulation
Authors: R.Stokes Peebles, Mark C. Liu, N.Franklin Adkinson, Lawrence M. Lichtenstein, Robert G. Hamilton
Journal: Journal of Allergy and Clinical Immunology (1998)

<h2>Abstract</h2> Background: Migration of eosinophils and release of eosinophil degranulation products into bronchoalveolar lavage fluid is a consistent finding in studies of late responses to allergen challenge in the lung. However, the mechanism of eosinophil activation and release of eosinophil products in vivo is unclear. Objective: We investigated the hypothesis that antigen-specific IgG, IgA, secretory IgA, or IgE is responsible for the eosinophil activation observed in the late-phase pulmonary reaction. Methods: Ragweed-specific IgE, IgA, secretory IgA, and IgG were measured by monoclonal antibody–based immunoassays in bronchoalveolar lavage (BAL) fluid and in serum from 19 asthmatic subjects allergic to ragweed and six healthy nonallergic control subjects before and 20 hours after segmental lung challenge with ragweed extract. Eosinophil cationic protein (ECP) was also measured in BAL fluid as a marker of eosinophil activation. Results: Most allergic asthmatic subjects had detectable levels of ragweed-specific IgE, IgA, and IgG in their serum and BAL fluid, whereas normal subjects had ragweed-specific IgA with no ragweed-specific IgE and little ragweed-specific IgG. IgA was the dominant ragweed-specific antibody isotype in BAL fluids. Ragweed-specific sIgA (<i>r<sub>s</sub></i> = 0.52, <i>p</i> = 0.02) and IgA (<i>r<sub>s</sub></i> = 0.50, <i>p</i> = 0.03) in BAL fluid after segmental lung challenge were significantly correlated with ECP. Ragweed-specific IgE and IgA in serum also correlated with ECP (<i>r<sub>s</sub></i> = 0.74, <i>p</i> < 0.001 and <i>r<sub>s</sub></i> = 0.48, <i>p</i> = 0.04, respectively). Conclusions: The correlation of allergen-specific IgA and IgE antibody levels with ECP as a marker of eosinophil degranulation suggests an important role for IgE antibodies in allergic pulmonary inflammation and a potential role for antigen-specific IgA in eosinophil degranulation in the lung after antigen challenge. (J Allergy Clin Immunol 1998;101:265-73.)
Donor Tissue Characteristics Influence Cadaver Kidney Transplant Function and Graft Survival but Not Rejection
Authors: Sita Gourishankar, Gian S. Jhangri, Sandra M. Cockfield, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Acute injury and age are characteristics of transplanted tissue that influence many aspects of the course of a renal allograft. The influence of donor tissue characteristics on outcomes can be analyzed by studying pairing, the extent to which two kidneys retrieved from the same cadaver donor manifest similar outcomes. Pairing studies help to define the relative role of donor-related factors (among pairs) versus non-donor factors (within pairs). This study analyzed graft survival for 220 pairs of cadaveric kidneys for the similarity of parameters reflecting function and rejection. It also examined whether the performance of one kidney was predicted by the course of its "mate," the other kidney from that donor. Parameters reflecting function showed sustained pairing posttransplantation, as did graft survival. In contrast, measures of rejection strongly affected survival but showed no pairing. Surprisingly, the survival of a kidney was predicted by the early performance of its mate, an observation we term the "mate effect." Six-month graft survival and renal function were reduced in grafts for which the mate kidney displayed any criteria for functional impairment (dialysis dependency, low urine output [≤1 L] in the first 24 h posttransplant or day-7 serum creatinine ≥ 400 μmol/L), even for kidneys which themselves lacked those criteria. Rejection measures did not demonstrate the mate effect. In conclusion, kidney transplant function is strongly linked to donor-related factors (age, brain death). In contrast, rejection affects survival and function, but it is not primarily determined by the characteristics of the donor tissue. Graft survival reflects both of these influences. E-mail: [email protected]
Spontaneous sarcoplasmic reticulum calcium release in rat and rabbit cardiac muscle: relation to transient and rested-state twitch tension.
Authors: A A Kort, E G Lakatta
Journal: Circulation Research (1988)

Scattered light intensity fluctuations (SLIF) (which monitor spontaneous Ca2+ release from the sarcoplasmic reticulum [SR]) and resting and twitch tension were measured during intervals after stimulation in rat and rabbit papillary muscles. For 1 to 5 seconds after stimulation of rat muscle bathed in 1.5 mM [Ca2+] (Cao), twitch and resting tension are depressed and SLIF are transiently abolished. SLIF and resting tension then recover simultaneously and monotonically but lag behind the restitution of twitch tension. In the absence of further stimulation, SLIF persist and the rested state twitch amplitude remains potentiated. When Cao is increased above 2.5 mM, the restitution of all parameters following stimulation is accelerated and becomes oscillatory; the lag of SLIF and resting tension restitution behind that of the twitch increases such that twitch amplitude increases, overshoots, and decreases to a nadir as SLIF and resting tension reach their initial maximum. In a given muscle, the maximum twitch amplitude occurs at approximately the same level of SLIF; when this level is exceeded, either transiently during monotonic or oscillatory recovery after stimulation in a given Cao or in the steady rested state by an increase in Cao, twitch tension decreases. Ryanodine (1 microM), caffeine (10 mM), or replacement of Cao with strontium abolishes SLIF and causes twitch amplitude to decay with rest. In contrast to rat, twitch amplitude in rabbit muscle bathed in physiological Cao decays with rest and SLIF are nonmeasurable at any interval following stimulation. When Cao is increased to 20 mM during rest, SLIF occur and the rest decay of the twitch is abolished. We interpret the parallel behavior of SLIF and rest potentiation to indicate that in the presence of SLIF, the average SR Ca2+ load within the tissue is high. Depolarization of a tissue exhibiting SLIF causes a large twitch but also a transient depletion of the average SR Ca2+ load. That the restitution of SLIF lags behind recovery of twitch amplitude suggests that the onset of spontaneous SR Ca2+ release requires a delay following SR Ca2+ replenishment. The simultaneous occurrence of spontaneous Ca2+ release in a sufficient number of cells places an upper limit on twitch amplitude either during recovery following stimulation or at rest.
Methods of Detection of Vascular Reactive Species
Authors: Margaret M. Tarpey, Irwin Fridovich
Journal: Circulation Research (2001)

The evanescent nature of reactive oxygen and nitrogen species, the multiple cellular mechanisms evolved to maintain these substances at low (submicromolar) concentrations within the vascular system, and the often multifaceted nature of their reactivities have made measurement of these compounds within the vasculature problematic. This review attempts to provide a critical description of some of the most common approaches to quantification of nitric oxide, superoxide, hydrogen peroxide, and peroxynitrite, with attention to key issues that may influence the utility of a particular assay when adapted for use in vascular cells and tissues.
The Breast Cancer Chemoprevention Debate
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2011)

T he latest data on breast cancer chemoprevention appeared in the New England Journal of Medicine on June 23, showing that exemestane (Aromasin), an aromatase inhibitor, reduced annual tumor risk by 65% compared with placebo. Generated by Paul Goss, Ph.D., a professor at Harvard Medical School and director of breast cancer research at Massachusetts General Hospital, in Boston, and colleagues, that finding drew widespread media attention after it was first announced on June 4 at the American Society of Clinical Oncology ’ s (ASCO) annual meeting in Chicago.
The Effects of Progressive General Anoxia on the Pulmonary Circulation
Authors: ALBERT HÜRLIMANN, CARL J. WIGGERS
Journal: Circulation Research (1953)

The effects of progressive anoxia on the hemodynamic changes in the pulmonary circuit were reinvestigated in anesthetized dogs. Evidence is presented that some increase in pulmonary arterial resistance takes place, but that the augmented output of the right ventricle is dominantly responsible for elevation of the pulmonary arterial pressure when anoxia affects the body as a whole.
Government says public backs homoeopathy despite lack of evidence
Authors: A. O'Dowd
Journal: BMJ (2009)

The government and its drug regulatory agency have admitted that no hard evidence exists that homoeopathic treatments work but say that public belief in them means they can continue to be recommended by doctors.

MPs on the parliamentary science and technology committee heard frank admissions from the Department of Health on 30 November as part of its inquiry into evidence to back the government’s policy on homoeopathy ( BMJ 2009;339:b5080, doi:10.1136/bmj.b5080).

The committee’s chairman, Phil Willis, the Liberal Democrat MP for Harrogate and Knaresborough, asked whether the government had any credible evidence that homoeopathy worked beyond a placebo effect.

The health minister Mike O’Brien said, …
Does Fast Dissociation From the Dopamine D<sub>2</sub> Receptor Explain the Action of Atypical Antipsychotics?: A New Hypothesis
Authors: Shitij Kapur, Philip Seeman
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Although atypical antipsychotics are becoming the treatment of choice for schizophrenia, what makes an antipsychotic "atypical" is not clear. This article provides a new hypothesis about the mechanism of action of atypical antipsychotics. METHOD: Published data regarding the molecular, animal model, neuroimaging, and clinical aspects of typical and atypical antipsychotics were reviewed to develop this hypothesis. Particular attention was paid to data regarding the role of the serotonin 5-HT2 and dopamine D4 receptors in atypicality. RESULTS: Neuroimaging data show that optimal dopamine D2 occupancy is sufficient to produce the atypical antipsychotic effect. Freedom from motor side effects results from low D2 occupancy, not from high 5-HT2 occupancy. If D2 occupancy is excessive, atypicality is lost even in the presence of high 5-HT2 occupancy. Animal data show that a rapid dissociation from the D2 receptor at a molecular level produces the atypical antipsychotic effect. In vitro data show that the single most powerful predictor of atypicality for the current generation of atypical antipsychotics is fast dissociation from the D2 receptor, not its high affinity at 5-HT2, D4, or another receptor. CONCLUSIONS: The authors propose that fast dissociation from the D2 receptor makes an antipsychotic more accommodating of physiological dopamine transmission, permitting an antipsychotic effect without motor side effects, prolactin elevation, or secondary negative symptoms. In contrast to the multireceptor hypotheses, the authors predict that the atypical antipsychotic effect can be produced by appropriate modulation of the D2 receptor alone; the blockade of other receptors is neither necessary nor sufficient.
Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34
Authors: D. R. Strother, L. Lafay-Cousin, J. M. Boyett, P. Burger, P. Aronin, L. Constine, P. Duffner, M. Kocak, L. E. Kun, M. E. Horowitz, A. Gajjar
Journal: Neuro-Oncology (2013)

The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children <3 years of age with newly diagnosed malignant brain tumors. Of 328 enrolled eligible patients, diagnoses were medulloblastoma (n = 112), ependymoma (n = 82), supratentorial primitive neuroectodermal tumor (sPNET, n = 38) and other malignant brain tumors (n = 96), and were randomized to 72 weeks of standard dose chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.
Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II, and calcium.
Authors: J Peters, K Münter, M Bader, E Hackenthal, J J Mullins, D Ganten
Journal: Journal of Clinical Investigation (1993)

The newly established rat strain TGR(mREN2)27 is a monogenetic model in hypertension research. Microinjecting the mouse Ren-2d renin gene caused it to become a stable part of the genome. The rats are characterized by fulminant hypertension, low plasma active renin, suppressed kidney renin, high plasma inactive renin, and high extrarenal transgene expression, most prominently in the adrenal cortex. Additionally, they exhibit significantly enhanced excretion of corticosteroids. Here we demonstrate that part of the plasma renin and most of the adrenal renin are transgene determined and that the adrenal renin is strongly activated. TGR(mREN2)27 adrenal cells may serve as a new tool to investigate the regulation and processing of Ren-2d-derived renin and its significance in hypertension and steroid metabolism. Adrenal renin in TGR(mREN2)27 is stimulated by 8-bromo-cAMP (8-Br-cAMP), angiotensin II (ANGII), and calcium. 8-Br-cAMP significantly stimulates active renin and prorenin release, as well as Ren-2d mRNA. Interestingly, within 60 min 8-Br-cAMP, ANGII, and calcimycin stimulate active renin, but not prorenin release. This indicates different intracellular pathways. An activated adrenal renin-angiotensin system in TGR (mREN2)27 as well as the lack of negative feedback on renin secretion by ANGII may be of pathophysiological significance in this hypertensive model.
Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension.
Authors: K Hermsmeyer
Journal: Circulation Research (1976)

The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension.
Major-histocompatibility-complex variation in two species of cichlid fishes from Lake Malawi.
Authors: H Ono, C O'hUigin, H Tichy, J Klein
Journal: Molecular Biology and Evolution (1993)

Lake Malawi in eastern Africa harbors > 500 endemic species of cichlid fishes, all of which are believed to have emerged from a single founding population in the past 2 Myr. Molecular characterization of differences among the species could provide important information about the nature of speciation in the period of adaptive radiation. Because of the close relationship, however, molecular variation among the species has been difficult to ascertain. In this communication, we provide evidence for extensive differences, in major-histocompatibility-complex (Mhc) class II genes, between two related species, Pseudotropheus zebra and Melanochromis auratus. We used specific primers to amplify and sequence intron 1 and exon 2 of the class II genes from 18 individuals. Although we found 20 different sequences among the 42 that we produced, there was not a single sequence shared by the two species. Thus the study suggests that different cichlid species of Lake Malawi have different profiles of class II alleles, presumably because the polymorphism present in the ancestral founding population segregated differentially into the various species. These results make Mhc genes an important tool for elucidating speciation.