tbuckley/cabot-search huggingface dataset:
Vitamin B<sub>12</sub>Malabsorption in Chronic Pancreatic Insufficiency
Authors: Phillip P. Toskes, John Hansell, James Cerda, Julius J. Deren
Journal: New England Journal of Medicine (1971)

Abstract 57Co-labeled vitamin B12 urinary excretion tests were performed on 22 patients with pancreatic exocrine insufficiency. Nine excreted less than 8 per cent of the orally administered vitamin in the urine within 24 hours. Known causes of vitamin B12 malabsorption such as intrinsic-factor deficiency, anti-intrinsic-factor antibodies, ileal disease and bacterial overgrowth were not present. The pH and total calcium content of ileal contents were similar in patients with pancreatic insufficiency whether they absorbed vitamin B12 normally or abnormally. No correlation was noted between malabsorption of the vitamin and fat malabsorption. Pancreatic extract (2 to 12 g) given to four of the nine patients with vitamin B12 malabsorption improved the urinary excretion test from a mean of 4.0 ± 0.64 (S.E.) per cent to 18.0 ± 2.63 per cent. Thus, some patients with pancreatic insufficiency show malabsorption of vitamin B12, and the pancreas may have a role in the absorption of this vitamin.
von Willebrand Factor–Cleaving Protease in Thrombotic Thrombocytopenic Purpura and the Hemolytic–Uremic Syndrome
Authors: Miha Furlan, Rodolfo Robles, Miriam Galbusera, Giuseppe Remuzzi, Paul A. Kyrle, Brigitte Brenner, Manuela Krause, Inge Scharrer, Volker Aumann, Uwe Mittler, Max Solenthaler, Bernhard Lämmle
Journal: New England Journal of Medicine (1998)

Thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor–cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders.
Refractory Hypotension in Man — Is This Irreversible Shock?
Authors: Louis L. Smith, Francis D. Moore
Journal: New England Journal of Medicine (1962)

AFTER a decade of reports on the phenomena of Shock in the dog, there is a need to return to studies in man. The histochemical sequences of tissue death in dog and man are doubtless similar. By contrast, the elaborately integrated circulatory responses of the whole organism, postural reflexes, dietary habits and bacteriology of the two species are strikingly different. The controlled experimental study of shock in the dog in the laboratory is quite simple to undertake, but sequential observations in the seriously injured human subject are notoriously difficult to make and require an elaborate organization if they are to . . .
The Origin and Development of Human Tumors Studied with Cell Markers
Authors: Philip J. Fialkow
Journal: New England Journal of Medicine (1974)

AMONG the more remarkable but least understood homeostatic mechanisms of higher organisms are those that govern tissue development, growth and repair. Considering the trillions of cells involved and the complexity and duration of these processes from fertilization until death, it is surprising that functional derangements such as neoplasia do not occur more frequently. Even so, cancer is one of the chief causes of human suffering and death, and, as such, has been the subject of intense research. In animals, such factors as genetic predisposition, viruses, radiation, chemicals, dietary components and hormones are known carcinogens, but they have been conclusively associated . . .
The Treatment of Multiple Myeloma
Authors: Alastair J.J. Wood, Raymond Alexanian, Meletios Dimopoulos
Journal: New England Journal of Medicine (1994)

Multiple myeloma accounts for 10 percent of hematologic cancers and kills approximately 10,000 Americans each year. The disease is more common in older persons, and blacks are affected twice as frequently as whites. The cause of multiple myeloma is unknown, and its extent, complications, sensitivity to drugs, and clinical course vary widely among patients. Since many aspects of the biology of this disease have recently been discussed elsewhere,1 this review will focus on treatment.Solitary Bone MyelomaApproximately 3 percent of patients have only one bone lesion and no evidence of bone marrow plasmacytosis. Fifty percent of such patients have . . .
OP05FUNCTIONAL ANALYSIS OF MULTI-DRUG RESISTANCE TRANSPORTER ABCB1 WHICH CORRELATES WITH POOR PROGNOSIS IN PAEDIATRIC EPENDYMOMA
Authors: D. Sabnis, L.C.D. Storer, J.-P. Kilday, J. Lowe, R.G. Grundy, I. Kerr, B. Coyle
Journal: Neuro-Oncology (2015)

INTRODUCTION: Paediatric ependymomas are aggressive drug-resistant tumours with a tendency to recur locally. This tendency is consistent with the Cancer Stem Cell hypothesis (CSCs) which states that there's a sub-population of therapy resistant cancer stem cells which remain refractory to treatment and recapitulate tumour growth. We hypothesised that drug efflux by the multi-drug resistance transporter ABCB1 is one of the resistance mechanisms upregulated in ependymoma CSCs. METHOD: ABCB1 immunohistochemistry (IHC) staining was performed on patient samples obtained from two trial cohorts; a chemotherapy-led infant trial (CNS9204) and a radiotherapy-led trial (CNS9904). Expression of ABCB1 in ependymoma derived cell lines and stem cell enriched neurospheres was assessed using RT-PCR. MTT assays and clonogenic assays were performed to assess potentiation of response to chemotherapy by ABCB1 inhibition using Verapamil and a novel agent, Vardenafil. The role of ABCB1 in tumour invasion was assessed by performing a 3-D migration assay. RESULTS: ABCB1 expression was significantly associated with reduced event -free survival (EFS) and overall survival (OS) in patients treated with chemotherapy (p-value-0.009 and 0.007 respectively). ABCB1 expression was restricted to a sub-population of cells and elevated in stem cell enriched neurospheres. ABCB1 inhibition potentiated response to chemotherapy (p = 0.0089) and reduced migration in the ependymoma derived BXD-1425 cell line. CONCLUSION: These findings constitute the first conclusive evidence that ABCB1 is capable of predicting clinical outcome in paediatric ependymoma patients where it plays an essential role in drug resistance and tumour invasion.
Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy
Authors: Eric Mariotte, Elie Azoulay, Lionel Galicier, Eric Rondeau, Fouzia Zouiti, Pierre Boisseau, Pascale Poullin, Emmanuel de Maistre, François Provôt, Yahsou Delmas, Pierre Perez, Ygal Benhamou, Alain Stepanian, Paul Coppo, Agnès Veyradier
Journal: The Lancet Haematology (2016)
Urinary Kallikrein Activity in the Hypertension of Renal Parenchymal Disease
Authors: John A. Mitas, Steven B. Levy, Rolf Holle, Ronald P. Frigon, Richard A. Stone
Journal: New England Journal of Medicine (1978)

To learn more about the regulation of blood pressure in renal parenchymal disease, 57 subjects (18 normal controls, 25 patients with essential hypertension and 14 with renal parenchymal disease and hypertension) were evaluated for peripheral renin activity, 24-hour urinary kallikrein activity and whole-blood volume. Blood volumes were significantly lower in patients with essential hypertension (P less than 0.001) and those with renal disease and hypertension (P less than 0.001) than in normotensive subjects. Renin activities (measured after the subjects were standing) were also lower in patients with essential hypertension and hypertension due to renal disease (P less than 0.01 and P less than 0.02, respectively). Kallikrein activity was similar in subjects with renal disease and those with hypertension (P less than 0.05) but markedly diminished in both groups as compared with normotensive subjects (P less than 0.001 and P less than 0.01, respectively) when glomerular filtration rates were taken into account. The kallikrein-kinin system may be involved in the hypertension associated with renal parenchymal disease.
Mathematical Analysis of the Establishment of Human Peripheral Blood Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C Rosenfeld, A Macieira-Coelho
Journal: JNCI Journal of the National Cancer Institute (1969)

The different hypotheses to explain the appearance of established cell lines obtained from human peripheral blood were examined. The clonal theory was rejected on a mathematical basis. One theory was supported by experimental data, and a general mathematical law for the establishment of leukocyte cultures was derived. This approach showed that establishment depended on three sequential forces: cell death, survival, and division.
Docetaxel (D) and oxaliplatin (DOCELOX) in advanced ovarian cancer (AOC): Preliminary safety results of a phase I-II
Authors: C. Tournigand, E. Carola, F. Maindrault Goebel, M. Bennamoun, M.-L. Garcia, H. Gervais, N. Perez, A. Plantade, C. Louvet, A. de Gramont
Journal: Journal of Clinical Oncology (2005)

5104 Background: docetaxel (D) and oxaliplatin are both active drugs in AOC (Vasey et al. J Natl Cancer Inst. 2004 and Misset et al. Ann Oncol. 2001). A phase I-II study was initiated to evaluate the tolerance and activity of the combination of oxaliplatin and D. Preliminary safety data are presented. Methods: Patients (pts) with a stage III or IV epithelial OC were included. Pts were either chemonaive (1st line) or relapsing > 6 mts after the last platin administration (2nd line, platinum sensitive). The 1st cycle was administered at the following doses: oxali 130 mg/m2 d1 and D 75 mg/m2 d1 (level 0). The D dose was increased to 85 mg/m2 for the following cycles, if no grade 3–4 toxicity (level 1). Cycles were repeated every 21 days. 6 cycles were planned. Lenograstim was administrered as secondary prophylaxis. Results: As of December 2004, 29 pts are included in 3 centers and 26 pts are evaluable for toxicity. 22 pts were treated in 1st line and 4 in 2nd line. In 1st line, 20 pts had a stage III and 2 a stage IV. In 2nd line, the 4 pts had a stage III, and they previously received paclitaxel and carboplatin as 1st line, with a median interval of 10.3 mts (6–32mts). The median age was 59 yrs. 15 pts (60%) received 6 cycles. 90 cy were delivered at level 0 (26 pts) and 29 at level 1 (7 pts). Grade ¾ tox by pt at level 0 were neutropenia (9pts, 35%) including 2 febrile neutropenia, anemia (2pts, 8%), diarrhea (3 pts, 11.5%) and thrombopenia (1pt, 4%). Grade ¾ toxicity by cycle at level 0 were neutropenia (11cy, 12%), anemia (2cy, 2%), diarrhea (4cy, 4%). Grade ¾ tox by pt at level 1 were neutropenia (5pts, 38%), diarrhea (1 pts, 8%), neuropathy (1pt, 8%) and nausea (1pt, 8%). Grade ¾ toxicity by cycle at level 1 were neutropenia (4cy, 14%), nausea (2cy, 7%), diarrhea (1cy, 3%), neuropathy (1cy, 3%). 18pts had gr 2 alopecia. Overall, only 2 pts had a gr 2 neuropathy and 1 pt a gr 3. Conclusions: The combination of docetaxel and oxaliplatin is well tolerated. Efficacy and final safety data will be available in May 05. No significant financial relationships to disclose.
CBIO-18ISOLATION OF HUMAN BRAIN TUMOUR INITIATING CELLS LEADING INVASION IN AN IN SITU ORGANOTYPIC SLICE CULTURE MIGRATION MODEL
Authors: Verena Leidgens, Xin Lu, Nina Patwary, Eugen Kerkhoff, Markus Riemenschneider, Ulrich Bogdahn, Arabel Vollmann-Zwerenz, Christoph Klein, Peter Hau
Journal: Neuro-Oncology (2015)

Glioblastomas (GBM) are characterized as highly malignant brain tumours, hallmarked by infiltrating tumour cells. Their pathogenesis may depend on Brain Tumour Initiating Cells (BTIC), according to recent publications. The subventricular zone and hippocampus are areas where BTICs may arise and migrate to distinct areas to initiate a tumour bulk via differentiation into the glial linage. In consequence, it is relevant to investigate the transdifferentiation, migratory and invasive potential of BTICs through the identification of molecules and pathways controlling the induction of invasion. Therefore, this study aimed to identify characteristics specific for invasion-driving GBM cells. Invasion of GBM cells was induced in an in situ model of organotypic brain slice cultures (OBSC), a valuable tool to visualize and analyse migration and invasion in a setting that simulates normal brain tissue conditions. Fluorescence tagged BTICs were inoculated in the hippocampal region of fresh brain slice cultures from new-born rats to monitor tumour cell invasion for three weeks. During this time, invasive cells emerge from the initial cell population, driving invasion into the surrounding tissue. Those invasive cells differ in morphology and behaviour from stationary cells remaining at the implantation site. An adapter was constructed to fit to a micromanipulator to isolate the different cell subpopulations from the OBSC. After cDNA library generation and subsequent microarray analysis, a detailed comparison has been made between both groups to compare gene expression profiles of genes associated with e.g. proliferation, invasion, cell-cell contacts, and stemness. Here, invasive cells showed a markedly distinct expression pattern in comparison to stationary cells. Identified transcription factors and their target gene expression will be verified in different BTIC subsets. Overall expressed genes specific for leader cells will be further characterized and regulated to manipulate the invasive behaviour and tumourigenicity of BTICs.
David Oliver: Progress on dementia in hospital
Authors: David Oliver
Journal: BMJ (2016)

England’s health secretary, Jeremy Hunt, used a speech in March to rehash the long running prime minister’s challenge to raise standards of care for people with dementia. All Hunt really said about acute hospitals was that patients with “high dependency” would get consultant ward rounds twice a day and that some may have dementia—part of his “seven day services” crusade.1 This was a missed opportunity to celebrate good, progressive government initiatives and to rise above party politics.

The national dementia strategy was started by the Labour government in 2009,2 but the 2010 …
Heparin for 5 Days as Compared with 10 Days in the Initial Treatment of Proximal Venous Thrombosis
Authors: Russell D. Hull, Gary E. Raskob, David Rosenbloom, Akbar A. Panju, Patrick Brill-Edwards, Jeffrey S. Ginsberg, Jack Hirsh, Gary J. Martin, David Green
Journal: New England Journal of Medicine (1990)

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography.
Role of Calcium in Gastric Hypersecretion, Parathyroid Adenoma and Peptic Ulcer
Authors: Robert F. Barreras, Robert M. Donaldson
Journal: New England Journal of Medicine (1967)

AS indicated in recent reviews,1 2 3 4 the nature of the frequently described association of peptic ulcer and hyperparathyroidism has not been clarified. The induction of hypercalcemia in man has been shown to lead to gastric hypersecretion.4 5 6 7 8 We report here studies carried out in a patient with parathyroid adenomas and peptic ulcer in whom marked basal gastric hypersecretion was observed. Parathyroidectomy led to restoration of normal serum calcium values and was accompanied by a fall in gastric secretion to normal levels. The subsequent induction of hypercalcemia was invariably associated with a rise in gastric secretion to the abnormal levels observed before operation. . . .
Serum Prostatic Acid Phosphatase and Cancer of the Prostate
Authors: William H. Fishman, C. D. Bonner, F. Homburger
Journal: New England Journal of Medicine (1956)

THE acid phosphatase content of malignant prostatic tissue is regarded as an example of the retention by the neoplastic growth of a biochemical characteristic of the fully differentiated tissue of origin. For fifteen years the serum acid phosphatase determination has been accepted as an adjuvant method for the diagnosis of cancer of the prostate. The findings of elevated values have been correlated with advanced cancer of the prostate with spread to bones and rarely with nonmetastatic disease. As a consequence, the finding of an elevated serum acid phosphatase in a patient with clinical evidence of localized cancer of the prostate . . .
Effects of Untreated Maternal Phenylketonuria and Hyperphenylalaninemia on the Fetus
Authors: Harvey L. Levy, Susan E. Waisbren
Journal: New England Journal of Medicine (1983)

We studied the effects of maternal phenylketonuria and hyperphenylalaninemia on 53 offspring from untreated pregnancies in 22 mothers who were identified by routine screening of umbilical-cord blood. The IQ of the offspring was significantly correlated with both maternal IQ (r = 0.83, P<0.001) and maternal blood phenylalanine level (r = -0.82, P<0.001), but with one exception, mental retardation in offspring was present only when the maternal blood phenylalanine level exceeded 1100 μmol per liter (18 mg per deciliter). Microcephaly in offspring was consistently present only when the maternal blood phenylalanine level exceeded 1200 μmol per liter (20 mg per deciliter). Congenital heart disease and other congenital anomalies were rare among offspring. The data suggest that severe atypical or classic phenylketonuria (blood phenylalanine level, >1100 μmol per liter) in the mother has a substantial cognitive effect on her offspring but that the effect of mild hyperphenylalaninemia may have been overstated in the past. (N Engl J Med 1983; 309: 1269–74.)
S80 Game on? The gamification of mHealth apps in the context of smoking cessation
Authors: M Ahmed, Y Sherwani, M Muntasir, A El-Hilly, S Iqbal, S Siddiqui, Z Al-Fagih, O Usmani, A Eisingerich
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Increasing emphasis has been placed on behavioural therapy in smoking cessation efforts. mHealth aims to join today’s arsenal of smoking cessation techniques. Many apps are utilising ‘gamification’ (the use of game design elements in non-game contexts) as a tool to drive positive behaviour change. However, a significant knowledge gap currently remains regarding how gamification can affect health behaviour. Our study seeked to elucidate the motivational mechanisms exploited by gamification in promoting positive health behaviours in the context of smoking cessation, with a view to generating recommendations on how to create effective gamified mHealth interventions. <h3>Methods</h3> We conducted a qualitative longitudinal study using a sample of 16 smokers divided into two cohorts. The first cohort used a non-gamified mHealth intervention, whilst the second used a gamified mHealth intervention. The added game components allowed us to isolate the effects of gamification. Each participant underwent 4 one-on-one, semi-structured interviews over a period of 5 weeks. Interviews were transcribed verbatim after which thematic analysis was undertaken. <h3>Results</h3> We observed that perceived behavioural control and intrinsic motivation acted as positive drivers to game engagement and consequently positive health behaviour. Importantly, external social influences exerted a negative effect. We identified three critical factors, whose presence was necessary for game engagement; purpose (explicit purpose known by the user), user alignment (congruency of game and user objectives), functional utility (a well-designed game). We summarise these findings in a framework (Figure 1), which we propose to guide the development of gamified mHealth interventions. <h3>Conclusions</h3> Our framework outlines the characteristics critical to consider when developing any gamified mHealth intervention to promote a particular health behaviour. Gamification holds the potential for low-cost, highly effective mHealth solutions that may replace or supplement the behavioural support component found in current smoking cessation programmes. Our proposed framework has been built on evidence specific to smoking cessation, but is versatile and can be extended to health interventions in other disease categories. Future research is now required to evaluate the effectiveness of the above framework directly against current behavioural support therapy interventions in smoking cessation.
Preclinical evaluation of apoptosis induction by the novel small molecule BCL-2 inhibitor, GX015–070, in ex vivo chronic lymphoid leukemia (CLL) cells
Authors: H. J. Olney, X. Weng, M. Watson, P. Beauparlant, D. Soulières, J. Viallet, M. Sarfati
Journal: Journal of Clinical Oncology (2005)

3149 Background: CLL is associated with loss of normal cellular apoptotic function. Apoptosis in cell lines has been identified with GX015–070 (GX), a small molecule antagonist of the BH3-binding groove of the BCL-2 family of proteins which is frequently overexpressed in cancers including CLL. This study evaluated GX induced apoptosis in CLL cells ex vivo correlating it with prognostic factors. Methods: Circulating lymphocytes were collected from patients (pts) with ≥ 20x109/L lymphocytes with no CLL treatment or red cell transfusions within 4 wks. Medical history was recorded. The diagnosis was confirmed with immunophenotyping by flow cytometry. CD38 was assessed in this analysis. The cytogenetic abnormalities del(11q), +12, del(13)(q14.3), del(13)(q34) & del(17p) were established by fluorescent in situ hybridization. Apoptosis was assessed with surface annexin V immunophenotyping in B cell enriched samples with positive glucocorticoid and negative DMSO controls. Results: 30 pts were recruited including 67% men with median age of 65 yrs (range 43–83). Rai stages were 6 stage 0; 8 stage 1; 6 stage 2; 4 stage 3; and 6 stage 4. Median lymphocyte count was 37.6x109/L (19.4–204.5). Prior treatment included 0–4 regiments (median 0). Previous treatments were alkylating agents (13%), purine analogues (13%), both (13%) and campath after both (3%). 33% of pts (n=10) expressed CD38. Cytogenetic analysis showed no abnormalities in 20%, del(11q) in 17%, +12 in 10%, -12 in 3%, del(13)(q14.3) in 53%, del(13)(q34) in 3% and no del(17p). ≥ 1 abnormality was seen in 4 pts. Apoptosis testing was performed and controls appropriate in 28 samples. All (100%) had significant early apoptosis with GX. A dose response to GX was found in all pts. The greatest % of annexin positive cells was observed at 6 hrs with 5 uM. In the last 12 pts, rescue from early apoptosis induction with IL-4 was observed in all glucocorticoid treated but in none of the GX treated cells. Conclusions: GX results in early and vigorous induction in vitro apoptosis of CLL cells. This population had both good & poor prognostic clinical factors. GX is one of the few agents where IL-4 co-treatment does not inhibit the induction of apoptosis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GeminX, GeminX Biotech