tbuckley/cabot-search huggingface dataset:
Points from Letters: The Paediatrician and the Future
Authors: J. Duguid
Journal: BMJ (1972)

<h3>Objective</h3> To compare the daily practice of two emergency departments (ED) in the Netherlands, where systemic inflammatory response syndrome (SIRS) criteria and quick Sequential Organ Failure Assessment (qSOFA) score are used differently as screening tools for culture-positive sepsis. <h3>Design</h3> A prospective cross-sectional multicentre study. <h3>Setting</h3> Two EDs at two European clinical teaching hospitals in the Netherlands. <h3>Participants</h3> 760 patients with suspected infection who met SIRS criteria or had a qualifying qSOFA score who were treated at two EDs in the Netherlands from 1 January to 1 March 2018 were included. <h3>Methods</h3> SIRS criteria and qSOFA score were calculated for each patient. The first hospital treated the patients who met SIRS criteria following the worldwide Surviving Sepsis Campaign protocol. At the second hospital, only patients who met the qualifying qSOFA score received this treatment. Therefore, patients could be divided into five groups: (1) SIRS+, qSOFA−, not treated according to protocol (reference group); (2) SIRS+, qSOFA−, treated according to protocol; (3) SIRS+, qSOFA+, treated according to protocol; (4) SIRS−, qSOFA+, not treated according to protocol; (5) SIRS−, qSOFA+, treated according to protocol. <h3>Primary and secondary outcome measures</h3> To prove culture-positive sepsis was present, cultures were used as the primary outcome. Secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission. <h3>Results</h3> 98.9% met SIRS criteria and 11.7% met qSOFA score. Positive predictive values of SIRS criteria and qSOFA score were 41.2% (95% CI 37.4% to 45.2%) and 48.1% (95% CI 37.4% to 58.9%), respectively. HRs were 0.79 (95% CI 0.40 to 1.56, p=0.500), 3.42 (95% CI 1.82 to 6.44, p&lt;0.001), 18.94 (95% CI 2.48 to 144.89, p=0.005) and 4.97 (95% CI 1.44 to 17.16, p=0.011) for groups 2–5, respectively. <h3>Conclusion</h3> qSOFA score performed as well as SIRS criteria for identifying culture-positive sepsis and performed significantly better for predicting in-hospital mortality and ICU admission. This study shows that SIRS criteria are no longer necessary and recommends qSOFA score as the standard for identifying culture-positive sepsis in the ED. <h3>Trial registration number</h3> NL8315.
PD-1 on dendritic cells impedes innate immunity against bacterial infection
Authors: Sheng Yao, Shengdian Wang, Yuwen Zhu, Liqun Luo, Gefeng Zhu, Sarah Flies, Haiying Xu, William Ruff, Megan Broadwater, In-Hak Choi, Koji Tamada, Lieping Chen
Journal: Blood (2009)
Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death
Authors: Kazuhiko Tsuruya, Toshiharu Ninomiya, Masanori Tokumoto, Makoto Hirakawa, Kohsuke Masutani, Masatomo Taniguchi, Kyoichi Fukuda, Hidetoshi Kanai, Kenji Kishihara, Hideki Hirakata, Mitsuo Iida
Journal: Kidney International (2003)
Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.
Authors: A E Calogero, W T Gallucci, P W Gold, G P Chrousos
Journal: Journal of Clinical Investigation (1988)

To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), beta-endorphin (beta-EP), alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine beta-lipotropin (ovine beta-LPH), and dexamethasone (DEX) upon unstimulated and serotonin- (5HT), acetylcholine- (ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10(-8) M range. ACTH had no detectable suppressive effect at 10(-8) M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion. beta-EP, alpha-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was beta-EP and the weakest was CLIP. Ovine beta-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion. In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.
CURRENT OUTCOMES FOR SUPERIOR FEMORAL ARTERY INTERVENTIONS: ROLE OF DIABETES AND RENAL INSUFFICIENCY
Authors: Christopher J. Smolock, Javier E. Anaya-Ayala, Jean Bismuth, Joseph J. Naoum, Hosam F. El-Sayed, Heitham Hassoun, Eric K. Peden, Alan B. Lumsden, Mark G. Davies
Journal: Journal of the American College of Cardiology (2011)
Immunoreactive atrial natriuretic peptide in ventricles, atria, hypothalamus, and plasma of genetically hypertensive rats.
Authors: H Ruskoaho, J Leppäluoto
Journal: Circulation Research (1988)

To evaluate the role of extra-atrial atrial natriuretic peptide (ANP) in volume and blood pressure regulation, the plasma, atrial, ventricular, and hypothalamic levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured simultaneously in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at the ages of 2, 6, and 12 months. Plasma IR-ANP in the 12-month-old, conscious SHR was significantly higher than that of the WKY (300 +/- 18 versus 200 +/- 20 pg/ml, p less than 0.05, n = 9), while no differences in plasma IR-ANP levels were found between the strains in younger rats. Acute volume expansion with saline (1.1 ml/100 g body wt) in hypertensive as well as in normotensive rats resulted in marked increases in right atrial pressure and plasma IR-ANP concentration. The older SHR had attenuated ANP release to volume loading as shown by the shift of the ANP versus right atrial pressure curve to the right. Right auricular IR-ANP concentration decreased, while that of left auricle increased with increasing age in both strains. No substantial differences were noted in auricular ANP concentration between SHR and WKY. However, the total atrial IR-ANP content (micrograms/atria) was consistently lower in SHR compared with WKY. In both ventricles, IR-ANP concentrations and contents increased with increasing age in WKY and SHR, but the ventricular levels of ANP were reduced in ventricles of the SHR heart compared with normotensive controls. The depletion of total ventricular IR-ANP was greatest in SHR with greatest ventricular hypertrophy and coincided with the attenuated ANP release to acute volume load. The increase of left but not right ventricular weight occurring secondary to 6 weeks minoxidil treatment was accompanied by higher ANP concentration in both strains. In contrast to the ventricles, the hypothalamic IR-ANP concentration was significantly increased in SHR compared with that of WKY and decreased in both strains after 6 weeks' treatment with antihypertensive drugs. Thus, ventricular and hypothalamic, as well as atrial, ANP respond to increased pressure overload in genetically hypertensive rats. Our results suggest that chronic stimulation of ANP release from ventricles is associated with depleted stores of ANP from both ventricles and reduced response to acute volume load. Our findings that ventricular ANP increased with increasing weight and in response to a hypertrophic stimulus in WKY and was decreased in SHR with severe ventricular hypertrophy suggest that ANP may locally have an inhibitory effect on the development of cardiac hypertrophy.
Frequency and clinical impact of preserved bispectral index activity during deep sedation in mechanically ventilated ICU patients
Authors: Pierre Trouiller, Pascal Fangio, Catherine Paugam-Burtz, Corinne Appéré-de-Vecchi, Paul Merckx, Nicolas Louvet, Sebastian Pease, Hervé Outin, Jean Mantz, Bernard De Jonghe
Journal: Intensive Care Medicine (2009)
Multiple Myeloma and Osteogenic Sarcoma in a Patient with Paget's Disease
Authors: Joseph Grader
Journal: JAMA (1961)

THE OCCURRENCE of multiple myeloma and Paget's disease in the same individual is rare. Between 1949 and 1953 of 1,000,000 patients admitted to veterans administration hospitals, 1,136 (1:880) were diagnosed as having Paget's disease and 900 (1:1,111) as having multiple myeloma. In only two cases did both diseases occur in the same patient.5This suggests a probable incidence of 1:500,000. Rosenkrantz and Gluckman,5in a review of the records of discharged patients from several city and voluntary hospitals, found 2 patients among 1,955,428 who were discharged with the combined diagnoses. In reviewing the literature, these authors collected 5 previous cases in addition to the 4 mentioned above. Schmorl6reported a case in 1912. Reich and Brodsky4reported a case in 1945 and mentioned one seen but not published by Snapper. Hanisch3described a patient in 1950, and Gross and Yelin2added one more in
Measles cases in England and Wales rise sharply in 2008
Authors: L. Eaton
Journal: BMJ (2009)

For a number of tumor types, including melanoma, positive clinical outcomes correlate with infiltration of T-cells into the tumor. However, failure to completely control disease progression often occurs, even with immune responses enhanced by checkpoint blockade or other immunotherapy. When T-cells fail to control tumor growth, the tumor infiltrating T lymphocytes (TIL) exhibit characteristics of exhaustion such as poor proliferation, poor effector function, and an increase in inhibitory receptor expression. Metabolic activity of T-cells contributes to differentiation and effector function, leading us to investigate the metabolic state of TIL. By flow cytometry, we find that CD8+ cytotoxic TIL have lower mitochondrial mass, as well as lower mitochondrial membrane potential, compared to effector CD8+ T-cells that respond to vaccination. We hypothesize that TIL are unable to effectively regulate their mitochondrial network, and it is likely that one or more fusion or fission machinery proteins has altered expression or can be manipulated to improve TIL function. We find that TIL have punctate mitochondria as compared to functional effector cells and hypothesize that elongation of the mitochondrial network will improve TIL function such as increasing the capacity for OXPHOS, which is seen in memory T cells with elongated mitochondrial networks. Using mice lacking the fission protein, Drp1, in T cells as a model of elongated mitochondria, we see increased mitochondrial membrane potential, spare respiratory capacity and OXPHOS as compared to WT cells with fission capability. We continue to investigate the effects of mitochondrial elongation of CD8+ cytotoxic TIL.
1217 Combination therapy for HCV affects the HIV viral load in patients receiving highly active antiretroviral therapy(HAART)
Authors: J KERTZNUS, E MOLINA, A REGEV, E SCHIFF
Journal: Hepatology (2003)

Zalcitabine (ddC), lamivudine (3TC), didanosine (ddI), stavudine (d4T), carbovir (CBV), zidovudine (AZT), tenofovir (PMPA) and its administrated form (tenofovir diisoproxyl fumarate, TDF), are nucleosides currently approved in HIV therapy. To facilitate pharmacokinetics studies, a specific reversed-phase high-performance liquid chromatography (HPLC) method was developed for their analysis in rat plasma. The method involved a quantitative recovery of these drugs from rat plasma by solid-phase extraction on Oasis® HLB Waters cartridges followed by optimised HPLC separation on an Atlantis™ dC18 column with acetic acid–hydroxylamine buffer (ionic strength 5 mM, pH 7)-acetonitrile elution gradient. Quantitation was performed by HPLC/UV at 260 nm. Linear calibration curves were obtained within a 30–10,000 ng/mL plasma concentration range. Correlation coefficients (r2) greater than 0.992 were obtained by least-squares regression and limits of quantification were in 30–90 ng/mL concentration range. Quantitative parameters (accuracy, intra-day repeatability and inter-day reproducibility) yielded satisfactory results. Finally, a new buffer, obtained with acetic acid and hydroxylamine, has been tested in HPLC/ESI-MS/MS and appears to be an efficient volatile buffer in the medium 5–7 pH range. Indeed, at pH 7 and low ionic strength (5 mM), its buffer capacity is one hundred times higher to that obtained for the usual acetic acid/ammonia buffer.
Weapons of mass destruction—threats and responses
Authors: Christine Gosden, Derek Gardener
Journal: BMJ (2005)

Weapons of mass destruction (WMD) include chemical, biological, and radiological agents with the potential to cause death at low doses and with serious long term health effects in survivors.This article provides general information relevant to all situations, from terrorist attacks in developed countries to conflict zones in Third World countries.WMD agents can be used to terrorise or subjugate populations and wreak economic damage.Many agents are cheap to produce and can be deployed in different ways.As well as overt use, such as in bombs or by aerial spraying, they can be used covertly such as in packages sent in the post, via animal vectors, or by poisoning of water and food supplies.
Disturbances of B cell homeostasis in takayasu arteritis and giant cell arteritis
Authors: B F Hoyer, H Mei, A Taddeo, R Biesen, G-R Burmester, A Radbruch, F Hiepe
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are an inflammation of the large arteries and their major branches. They have been considered distinct disorders based on their clinical features, age of onset and ethnic distribution. But the histopathology of arterial lesions and imaging studies suggest similar pathogenetic mechanisms in these diseases. Since the authors have recently shown disturbances in the B cell homeostasis in patients with active TAK the aim of this study was to analyse circulating B cell subpopulations in patients with GCA as compared to those with TAK. <h3>Methods</h3> Peripheral blood mononuclear cells from six patients with active TAK and six with inactive disease, 16 patients with GCA (eight with active and eight with inactive disease) and 12 healthy controls were analysed by flow cytometry for the expression of CD27, CD19, CD20, MHCII, CD3, CD8 and CD4. Plasma cell population is considered CD20−/CD19+/CD27+++. Newly generated plasmablasts express additionally MHC class II. CD19+/CD20+/CD27+ cells were considered as memory B cells and their CD27 low counterpart as naive B cells. <h3>Results</h3> Patients with active TAK and GCA showed significantly higher frequencies of plasma cells (among all CD19+ B cells) than in inactive patients (p=0.02 and 0.029, respectively) and healthy controls. The absolute plasma cell numbers were increased in TAK patients (p=0.0015) but not in GCA. Active TAK patients showed also elevated circulating plasmablasts in comparison with patients in remission (p=0.0053). The frequency of plasma cells in the blood correlated significantly with the disease activity according to the NIH criteria (r=0.73 and p=0.069). In contrast to TAK, active GCA patients exhibited a significant reduction of the memory B cell subset versus inactive patients (p=0.028). Disturbances of T cell subset were not observed. <h3>Conclusions</h3> The findings suggest different roles of B cells in the pathogenesis of TAK versus GCA. Circulating plasma cells/plasmablasts may serve as biomarker of disease activity in TAK and provide indication for a B cell and plasma cell directed therapy.
Extensive purpura in a patient with paroxysmal nocturnal hemoglobinuria
Authors: Takeshi Nara, Sachiyo Kimori, Hiroshi Nakamichi, Yoshihiro Ikeda, Teruaki Akaogi, Mizuho Kurita, Ryouzou Okuda, Norito Katoh, Saburou Kishimoto
Journal: Journal of the American Academy of Dermatology (2005)
AT-28 * LONG-TERM SURVIVAL (OVER 15 YEARS) OF PATHOLOGICALLY CONFIRMED RECURRENT GLIOBLASTOMA MULTIFORME: A CASE REPORT
Authors: T. Janicki, G. Burzynski, S. Burzynski
Journal: Neuro-Oncology (2014)

Recurrent GBM carries poor prognosis with no standard therapy available. A 46-year-old Caucasian female underwent a partial resection of the tumor revealing a pathologic diagnosis of GBM. The patient then received radiation therapy (RT) at the dose of 5940 cGy over a six-week duration. After four months, she underwent a Gamma Knife procedure. Seven months later, she developed recurrence and underwent a second partial tumor resection. The pathology diagnosis again confirmed GBM. Magnetic resonance imaging (MRI) performed within one month revealed a recurrent tumor. A month later, treatment with IV infusions of antineoplastons A10 and AS2-1 (ANP) was initiated based on Special Exception into Protocol BT-20. During the baseline evaluation, the patient complained of marked weakness, short memory loss, frequent aura, loss of coordination, nausea, dizziness, difficulty walking, and speech problems. The dosage of A10 was gradually increased to 10.44 g/kg/d and AS2-1 to 0.17 g/kg/d. IV ANP was discontinued after 18.5 months due to complete response (CR). The only adverse event possibly related to the treatment was grade 1 skin rash, which resolved spontaneously. After stopping treatment with IV ANP, the patient started taking ANP A10 and AS2-1 orally (0.14 g/kg/d each). All treatments were discontinued after 31 months. The patient made a substantial recovery; she was able to walk without assistance and made progress in speech therapy. The baseline MRI revealed a right temporal enhancing lesion of 1.5 cm x 1.3 cm. Beginning fourteen months after the treatment start (10/14/1999), the MRI images showed a CR. Currently the patient is free from tumor recurrence, but had experienced some deterioration of her mental capacity due to chronic post-radiation toxicity. Her overall survival and progression-free survival is over 15 years.
Intravenous infusion of frusemide as treatment for ascites in malignant disease.
Authors: S A Amiel, A M Blackburn, R D Rubens
Journal: BMJ (1984)

4 observations d'ascite due a des tumeurs malignes avancees (ovaire, metastases hepatiques de cancer du sein) dans lesquelles la perfusion continue de frusemide a amene un soulagement rapide et durable
Consultation over children's heart surgery was unfair to Royal Brompton, judge rules
Authors: C. Dyer
Journal: BMJ (2011)

A consultation exercise that proposed closing the children’s heart surgery unit at the Royal Brompton Hospital in London has been quashed by the High Court in London, in a landmark ruling.

The NHS’s Joint Committee of Primary Care Trusts, which is conducting the consultation on “safe and sustainable children’s congenital cardiac services,” immediately announced its intention to appeal, claiming that the judge had “misunderstood” the review process.

The consultation came after a recommendation from the 2001 report of the public inquiry into deaths of children undergoing heart surgery at Bristol Royal Infirmary, chaired by Ian Kennedy. The report suggested an investigation to ensure that surgery should not be carried out in hospitals where the low volume of patients or other factors made it unsafe.

After a 2007 report that recommended fewer and larger …
Catheter ablation of ventricular tachycardia with intracardiac shocks: results in 33 patients.
Authors: F Morady, M M Scheinman, L A Di Carlo, J C Davis, J M Herre, J C Griffin, S A Winston, M de Buitleir, C B Hantler, J A Wahr
Journal: Circulation (1987)

Catheter electrical ablation of ventricular tachycardia (VT) was attempted in 33 patients who had recurrent unimorphic VT refractory to 3.7 +/- 1.2 (mean +/- SD) antiarrhythmic drugs. Their mean age was 56 +/- 14 years. Twenty-two patients had coronary artery disease, six had other types of heart disease, and five had no structural heart disease. The mean left ventricular ejection fraction was 0.34 +/- 0.17. Thirty patients had only one documented morphologic type of spontaneous VT, whereas three patients had more than one. One to four shocks of 100 to 300 J each were delivered to the endocardial exit site of VT, as identified by endocardial activation mapping and pace-mapping. In each patient endocardial activation at the exit site of VT preceded the onset of the QRS complex (mean activation time -50 +/- 30 msec). Pace-mapping was possible in 26 patients, and in all but two patients the QRS complexes during VT and during pacing at the exit site of VT were very similar in at least 10 of 12 electrocardiographic leads. In 29 patients, shocks were delivered between an endocardial electrode (cathode) and a patch electrode on the chest wall (anode). Seven patients (including three who first received shocks using an external anode) whose VT originated in the septum received transseptal shocks between two electrodes positioned on either side of the septum. The procedure was successful in 15 patients (45%), who had no recurrence of VT either on no antiarrhythmic therapy or on the same regimen that was ineffective before ablation, over a follow-up period of 15.5 +/- 10 months (range 5 to 35). The ablation attempt was unsuccessful in 18 patients (55%). There were no significant differences in clinical and electrophysiologic variables between patients with and without a successful outcome. Seven nonfatal complications occurred in six patients: sustained nonclinical VT immediately after the shock, ventricular fibrillation on days 5 and 6 after ablation, neurologic deficits (n = 2), atrioventricular block (n = 2), and brachial artery thrombosis. In conclusion, catheter electrical ablation of VT has modest efficacy and is relatively safe in a selected group of patients who have predominantly one configuration of unimorphic VT.
DISEASE AND HOSPITALS OF THE INTERIOR OF SOUTH AFRICA.
Authors: NICHOLAS SENN
Journal: JAMA (1906)

<h3>SANITATION IN JOHANNESBURG—DISEASES OF CENTRAL SOUTH AFRICA.</h3> The great diamond mines of Kimberley and the richest gold mines in the world at Johannesburg are only fifteen hours apart by rail. Nature has deposited here within this limited space her richest treasures in the very heart of what was but a few years ago the Dark Continent. These mining cities are situated on the highest elevation of the interior plateau of South Africa, and the diseases prevailing here are representative of the diseases of that part of Africa. Thanks to Dr. Charles Porter, the health officer of Johannesburg, I was given every facility to get a good insight into this subject, besides familiarizing myself with sanitary matters in the city of Johannesburg. The city has about 210,000 inhabitants, 80,000 whites, the same number of negroes, and 50,000 Chinese. Dr. Porter is the busiest man in the city. He has made sanitation
Points: Measuring faecal fat
Authors: D M Merrington
Journal: BMJ (1988)

gresses more rapidly in this group is in dispute.Although we are unlikely to find premalignant disease in the sexually active girls under 16, we think that cytological screening is useful to educate them about the need for regular cervical smears.These patients are likely to have many sexual partners, have a high prevalence of sexually trans- mitted diseases (770/o-A J Robinson, unpublished data), and be at high risk of developing cervical intraepithelial neoplasia.